August 8, 2007
August 21, 2006
Molecular biology in prostate cancer.
Molecular biology in prostate cancer.
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Molecular biology in prostate cancer.
Clin Transl Oncol. 2006 Mar;8(3):148-52
Authors: Cansino Alcaide JR, Mart nez-Pi eiro L
Genes involved in cancer generation are usually tumor suppressors and oncogenes. Progressive genetic alterations in these genes are involved in the mechanisms of tumorigenesis. In prostate cancer, additionally several chromosomal loci that should harbor mutated genes have been proposed. Some genes have been found altered in prostate cancer, such as PTEN, TP53, AR, RNASEL (HPC1), ELAC2 (HPC2), CDKN2A and MSR1 and those can be natural targets for new strategies of treatment. Besides, gene therapy has been suggested to be suitable for prostate cancer treatment. This approach includes ex vivo corrective therapy, suicide, and antisense therapy.
PMID: 16648113 [PubMed - indexed for MEDLINE]
August 9, 2006
Prostate Cancer Genetics; +158 new citations
Prostate Cancer Genetics; +158 new citations
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June 13, 2006
Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers.
Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers.
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Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers.
Prostate. 2006 Jun 1;66(8):801-10
Authors: Krajewska M, Turner BC, Shabaik A, Krajewski S, Reed JC
BACKGROUND: Differences in tumor behavior, ranging from indolent to aggressive, create a need for novel prognostic biomarkers. BAG-1 is a co-chaperone that regulates the activity of Hsp70, Bcl-2, Raf-1, growth factor, and steroid receptors (e.g., the Androgen Receptor). METHODS: Using immunohistochemical method, we explored BAG-1 expression in prostate cancers and its association with clinicopathological parameters. RESULTS: BAG-1 immunostaining was elevated in prostate cancer compared to normal prostatic epithelium. Higher nuclear BAG-1 in hormone-refractory (n = 34) compared to localized untreated tumors (n = 58) (P < 0.0001) suggested that upregulation of the nuclear isoform may contribute to disease progression. In 64 early-stage patients (T2N0M0) treated with external-beam irradiation, cytosolic BAG-1 correlated with higher pretreatment levels of serum Prostate specific antigen (P = 0.04) and shorter time to disease progression (P = 0.00004). CONCLUSIONS: Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer.
PMID: 16482527 [PubMed - indexed for MEDLINE]
June 5, 2006
Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancer.
Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancer.
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Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancer.
Urology. 2006 May;67(5):1001-6
Authors: Srinivas S, Krishnan AV, Colocci N, Feldman D
OBJECTIVES: To assess the effect of triamcinolone administration on the serum prostate-specific antigen (PSA) response and the time to progression in patients with androgen-independent prostate cancer (AIPC). METHODS: Patients with AIPC were prospectively treated with oral triamcinolone 4 mg twice daily, and their serum PSA and cortisol levels were measured monthly. Patients with greater than 25% increases in serum PSA from baseline were considered to have progressive disease and were removed from the study. Those patients who had a decrease in serum PSA levels or stable disease continued in the study until disease progression. Bone scans were obtained every 12 weeks and at progression. RESULTS: Twenty-four patients with AIPC were treated from November 2002 to June 2004. A partial response with a more than 50% decrease in serum PSA level was seen in 29%. Another 21% achieved stable disease. No statistically significant difference was found in the time to progression in the partial responders and patients with stable disease. The median time to progression in both groups was 7.5 months. Treatment was well tolerated without any grade 3 or 4 toxicity. CONCLUSIONS: Oral triamcinolone was well tolerated by patients with AIPC, with 50% of the patients exhibiting a good response to therapy in terms of serum PSA level and time to progression.
PMID: 16698360 [PubMed - indexed for MEDLINE]
May 24, 2006
Expression and implication of hypoxia inducible factor-1alpha in prostate neoplasm.
Expression and implication of hypoxia inducible factor-1alpha in prostate neoplasm.
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Expression and implication of hypoxia inducible factor-1alpha in prostate neoplasm.
J Huazhong Univ Sci Technolog Med Sci. 2004;24(6):593-5
Authors: Hao P, Chen X, Geng H, Gu L, Chen J, Lu G
To study the expression of hypoxia inducible factor-1alpha (HIF-1alpha) protein in prostate cancer (Pca) and its biological significance, the expression of HIF-1alpha was assayed by means of immunohistochemical technique in 42 prostate cancer, 12 prostatic intraepithelial neoplasm (PIN) and 9 normal prostate tissue (NP) specimens. Western blot was used to examine the expression of HIF-1alpha in prostate cancer cell line (PC-3M) induced by different oxygen tension. HIF-1alpha expression was positive in 33 Pca and 9 PIN specimens, and the positive rate of HIF-1alpha was higher in distant metastasis patients than in patients without metastasis of prostate cancer (P<0.05), while there was no expression of HIF-1alpha in NP. The level of HIF-1alpha in PC-3M significantly increased with the decrease of oxygen tension (P<0.01). Overexpression of HIF-1alpha is the preliminary event of the formation of Pca, which may induce carcinoma into malignant phenotype. Thus it may serve as an early diagnosis marker and the novel target for Pca treatment.
PMID: 15791851 [PubMed - indexed for MEDLINE]
May 15, 2006
Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin.
Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin.
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Overexpression of ecto-protein kinases in prostasomes of metastatic cell origin.
Prostate. 2006 May 15;66(7):675-86
Authors: Babiker AA, Ronquist G, Nilsson B, Ekdahl KN
BACKGROUND: Prostasomes are secretory granules produced, stored, and released by the glandular epithelial cells of the prostate. They express numerous enzymes whose physiological roles have so far not been fully evaluated. In this study, we investigated the expression and function of prostasomal protein kinases and ATPase. METHODS: The protein kinase activities of prostasomes isolated from seminal fluid and malignant prostate cell lines (PC-3, DU145, and LNCaP) were investigated using the model phosphorylation substrates histone and casein, as well as the plasma proteins C3 and fibrinogen, in combination with specific protein kinase inhibitors. The prostasomal ATPase activity was also evaluated. The expression of protein kinases and ATPase on prostasomes was verified by flow cytometry. RESULTS: Prostasomes (intact or solubilized with octylglucoside or saponin) from prostate cancer cells had higher expression of protein kinases A, C, and casein kinase II compared to prostasomes isolated from seminal plasma, resulting in higher phosphorylation of both exogenous and endogenous substrates. Using intact prostasomes, it was found that prostasomes of metastatic origin had lower ATPase activity, resulting in higher residual ATP available for the phosphorylation reaction. Finally, complement component C3 and fibrinogen (two proteins whose activities are modulated by phosphorylation) were identified as physiologically relevant phosphorylation substrates. CONCLUSIONS: These results indicate that prostasomes are capable of modifying proteins possibly involved in the innate response by extracellular phosphorylation mediated by ecto-kinases. This is a novel mechanism by which prostatic malignant cells may interact with their environment.
PMID: 16425202 [PubMed - indexed for MEDLINE]
May 4, 2006
Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?
Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?
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Gene expression studies in prostate cancer tissue: which reference gene should be selected for normalization?
J Mol Med. 2005 Dec;83(12):1014-24
Authors: Ohl F, Jung M, Xu C, Stephan C, Rabien A, Burkhardt M, Nitsche A, Kristiansen G, Loening SA, Radoni A, Jung K
Using quantitative reverse transcription-polymerase chain reaction (RT-PCR), reference genes are utilized as endogenous controls for relative quantification of target genes in gene profiling studies. The suitability of housekeeping genes for that purpose in prostate cancer tissue has not been sufficiently investigated so far. The objective of this study was to select from a panel of 16 potential candidate reference genes the most stable genes for gene normalization. Expression of mRNA encoding ACTB, ALAS1, ALB, B2M, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, POLR2A, PPIA, RPL13A, SDHA, TBP, UBC, and YWHAZ was examined in matched, microdissected malignant and nonmalignant tissue specimens obtained from 17 nontreated prostate carcinomas after radical prostatectomy by real-time RT-PCR. The genes studied displayed a wide expression range with cycle threshold values between 16 and 37. The expression was not different between samples from pT2 and pT3 tumors or between samples with Gleason scores <7 and >or=7 (P>0.05). ACTB, RPL13A, and HMBS showed significant differences (P<0.02 at least) in expressions between malignant and nonmalignant pairs. All other genes did not differ between the matched pairs, and the software programs geNorm and NormFinder were used to ascertain the most suitable reference genes from these candidates. HPRT1, ALAS1, and K-ALPHA-1 were calculated by both programs to be the most stable genes covering a broad range of expression. The expression of the target gene RECK normalized with HRPT1 alone and with the normalization factors generated by the combination of these three reference genes as well as with the unstable genes ACTB or RPL13A is given. That example shows the significance of using suitable reference genes to avoid erroneous normalizations in gene profiling studies for prostate cancer. The use of HPRT1 alone as a reference gene shown in our study was sufficient, but the normalization factors generated from two (HRPT1, ALAS1) or all three genes (HRPT1, ALAS1, K-ALPHA-1) should be considered for an improved reliability of normalization in gene profiling studies of prostate cancer.
PMID: 16211407 [PubMed - indexed for MEDLINE]
May 2, 2006
RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory region.
RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory region.
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RUNX1 (AML-1) and RUNX2 (AML-3) cooperate with prostate-derived Ets factor to activate transcription from the PSA upstream regulatory region.
J Cell Biochem. 2006 Jan 1;97(1):1-17
Authors: Fowler M, Borazanci E, McGhee L, Pylant SW, Williams BJ, Glass J, Davis JN, Meyers S
The RUNX transcription factors (RUNX1, RUNX2, and RUNX3) play essential roles in hematopoiesis and skeletal development. Consistent with these roles in differentiation and cell cycle, the activity of both RUNX1 and RUNX3 is perturbed in cancer. To determine a role for the RUNX factors in prostate biology, we investigated the expression of RUNX factors in prostate epithelial cell lines and normal prostate tissue. RUNX1, RUNX2, and RUNX3 were expressed in both normal prostate tissue and an immortalized, non-transformed cell line. We found that prostate cancer-derived cell lines expressed RUNX1 and RUNX2, but not RUNX3. Next, we sought to identify prostate-specific genes whose expression could be regulated by RUNX proteins. Four consensus RUNX sites are located within the prostate-specific antigen (PSA) regulatory region. Chromatin immunoprecipitation (ChIP) analysis showed that RUNX1 is specifically bound to the PSA regulatory region in LNCaP cells. RUNX1 and RUNX2 activated the PSA regulatory region alone or cooperatively with prostate-derived ETS factor (PDEF) and RUNX1 physically associated with PDEF. Taken together, our results suggest that RUNX factors participate in prostate epithelial cell function and cooperate with an Ets transcription factor to regulate PSA gene expression.
PMID: 16237704 [PubMed - indexed for MEDLINE]
April 18, 2006
Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population.
Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population.
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Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population.
Cancer Invest. 2006 Feb;24(1):41-5
Authors: Silig Y, Pinarbasi H, G nes S, Ayan S, Bagci H, Cetinkaya O
Prostate cancer is the most common cancer among men in many countries. Although the etiology of prostate cancer largely is unknown, both genetic and environmental factors may be involved. Advanced age, androgen metabolism, and heredity-race have been reported to be possible risk factors. On the other hand, several studies indicate that genetic polymorphisms in biotransformation enzymes play a role in prostate cancer development. In this study, association of the prostate cancer risk with genotype frequencies of the Phase I (CYP1A1) and Phase II (GSTM1 and GSTT1) biotransformation enzymes was investigated in 321 Turkish individuals (152 prostate cancer patients and 169 age-matched male controls). The presence or absences of the GSTM1 and GSTT1 genes were determined by a PCR-based method. Genotypes of CYP1A1 were determined by MspI-RFLP. The prevalence of GSTM1 null genotype in the cases was 64 percent, compared to 31 percent in the control group, indicating a strong association (OR = 4.08, 95%CI = 2.50-6.69). No association was observed between either GSTT1 null genotype or CYP1A1 polymorphism and prostate cancer incidence. No statistically significant association was observed between smoking status of the patients and any of the polymorphisms studied. In conclusion, results of this study indicate that only the GSTM1 null genotype may play an important role as a risk factor for prostate cancer development in Turkish population.
PMID: 16466991 [PubMed - indexed for MEDLINE]
April 12, 2006
MCM7 amplification and overexpression are associated with prostate cancer progression.
MCM7 amplification and overexpression are associated with prostate cancer progression.
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MCM7 amplification and overexpression are associated with prostate cancer progression.
Oncogene. 2006 Feb 16;25(7):1090-8
Authors: Ren B, Yu G, Tseng GC, Cieply K, Gavel T, Nelson J, Michalopoulos G, Yu YP, Luo JH
The genomic DNA profiles of prostate cancers with aggressive features were compared to the profiles of matched normal DNA to identify genes that are selectively amplified in the cancer cells. One of the identified genes, MCM7, which is a component of the DNA replication licensing complex, has been studied extensively both at the DNA and protein levels in human prostate tissues. Approximately half of the prostate cancer specimens studied showed MCM7 gene amplification, and 60% of the aggressive prostate cancer specimens had increased MCM7 protein expression. Amplification or overexpression of MCM7 was significantly associated with relapse, local invasion and a worse tumor grade. Constitutive expression of MCM7 in a human prostate cancer cell line, DU145, resulted in markedly increased DNA synthesis and cell proliferation compared to vector-only controls, and an increased cell invasion in vitro. Indeed, MCM7 overexpression produced primary tumors 12 times larger than vector-only controls and resulted in a rapid demise of mice bearing those tumors. These studies implicate MCM7, and the DNA replication licensing gene family, in prostate cancer progression, growth and invasion.
PMID: 16247466 [PubMed - indexed for MEDLINE]
March 21, 2006
Gene delivery and gene therapy of prostate cancer.
Gene delivery and gene therapy of prostate cancer.
Related Articles Gene delivery and gene therapy of prostate cancer. Expert Opin Drug Deliv. 2006 Jan;3(1):37-51 Authors: Kaliberov SA, Buchsbaum DJ Surgery, radiation or hormonal therapy are not adequate to control prostate cancer. Clearly, other novel treatment approaches, such as gene therapy, for advanced/recurrent disease are desperately needed to achieve long-term local control and particularly to develop effective systemic therapy for metastatic prostate cancer. In the last decade, significant progress in gene therapy for the treatment of localised prostate cancer has been demonstrated. A broad range of different gene therapy approaches, including cytolytic, immunological and corrective gene therapy, have been successfully applied for prostate cancer treatment in animal models, with translation into early clinical trials. In addition, a wide variety of viral and nonbiological gene delivery systems are available for basic and clinical research. Gene therapy approaches that have been developed for the treatment of prostate cancer are summarised. PMID: 16370939 [PubMed - indexed for MEDLINE]
March 16, 2006
The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes.
The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes.
Related Articles The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer. 2006 Jan;45(1):31-41 Authors: Diep CB, Kleivi K, Ribeiro FR, Teixeira MR, Lindgjaerde OC, Lothe RA To identify chromosomal aberrations that differentiate among the Dukes' stages of colorectal cancer (CRC) as well as those that are responsible for the progression into liver metastases, we performed a meta-analysis of data obtained from 31 comparative genomic hybridization (CGH) studies comprising a total of 859 CRCs. Individual copy number profiles for 373 primary tumors and 102 liver metastases were recorded and several statistical analyses, such as frequency, multivariate logistic regression, and trend tests, were performed. In addition, time of occurrence analysis was applied for the first time to copy number changes identified by CGH, and each genomic imbalance was thereby classified as an early or late event in colorectal tumorigenesis. By combining data from the different statistical tests, we present a novel genetic pathway for CRC progression that distinguishes the Dukes' stages and identifies early and late events in both primary carcinomas and liver metastases. Results from the combined analyses suggest that losses at 17p and 18 and gains of 8q, 13q, and 20 occur early in the establishment of primary CRCs, whereas loss of 4p is associated with the transition from Dukes' A to B-D. Deletion of 8p and gains of 7p and 17q are correlated with the transition from primary tumor to liver metastasis, whereas losses of 14q and gains of 1q, 11, 12p, and 19 are late events. We supplement these findings with a list of potential target genes for the specific alterations from a publicly available microarray expression dataset of CRC. PMID: 16145679 [PubMed - indexed for MEDLINE]
March 15, 2006
Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
Related Articles Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism. J Clin Endocrinol Metab. 2006 Feb;91(2):687-93 Authors: Jakobsson J, Ekstr m L, Inotsume N, Garle M, Lorentzon M, Ohlsson C, Roh HK, Carlstr m K, Rane A CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes. PMID: 16332934 [PubMed - indexed for MEDLINE]
March 12, 2006
Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans.
Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans.
Related Articles Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol. 2006 Jan;175(1):108-12; discussion 112 Authors: Chen L, Ambrosone CB, Lee J, Sellers TA, Pow-Sang J, Park JY PURPOSE: XRCC1 and APE1 are enzymes involved in the repair of DNA strand breaks and base damage that arise from various endogenous and exogenous oxidants. We determined whether polymorphisms in XRCC1 and APE1 increase the risk of prostate cancer. MATERIALS AND METHODS: We performed a case-control study in 228 white American men, 124 black American men, and 335 age, sex and race matched controls. Polymorphisms at codon 399 in XRCC1, and at codons 51 and 148 in APE1 were determined using an restriction fragment length polymorphism method. Frequencies were compared between cases and controls. RESULTS: A significantly increased risk of prostate cancer was observed in white men with the XRCC1(399Gln) allele (OR 1.6, 95% CI 1.1 to 2.4). When APE1 and XRCC1 polymorphisms were evaluated together, we found an increased risk of the XRCC1(399Arg/Gln+Gln/Gln)/APE1(51Gln/Gln) (OR 4.0, 95% CI 1.3 to 12.5) and XRCC1(399Arg/Gln+Gln/Gln)/APE1(148Asp/Asp) (OR 2.9, 95% CI 1.4 to 6.1) genotypes in white men. Significant associations were found between combined genotypes and prostate cancer risk with a dose-effect relationship in white men (trend test p = 0.035 and 0.039, respectively). No significant associations were observed between polymorphisms in these genes and prostate cancer risk in black men. CONCLUSIONS: Our results suggest that inherited variability in DNA repair capacity, as reflected by polymorphisms in XRCC1 and APE1, is a risk factor for prostate cancer. PMID: 16406883 [PubMed - indexed for MEDLINE]
February 27, 2006
Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer.
Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer.
Related Articles Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer. Cancer Res. 2006 Jan 1;66(1):385-92 Authors: McCabe MT, Low JA, Daignault S, Imperiale MJ, Wojno KJ, Day ML Transcriptional silencing of tumor suppressor genes by DNA methylation plays an important role in tumorigenesis. These aberrant epigenetic modifications may be mediated in part by elevated DNA methyltransferase levels. DNA methyltransferase 1 (DNMT1), in particular, is overexpressed in many tumor types. Recently, we showed that Dnmt1 is transcriptionally regulated by E2F transcription factors and that retinoblastoma protein (pRb) inactivation induces Dnmt1. Based on these observations, we investigated regulation of Dnmt1 by polyomavirus oncogenes, which potently inhibit the pRb pocket protein family. Infection of primary human prostate epithelial cells with BK polyomavirus dramatically induced Dnmt1 transcription following large T antigen (TAg) translation and E2F activation. For in vivo study of Dnmt1 regulation, we used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which expresses the SV40 polyomavirus early region, including TAg, under control of a prostate-specific promoter. Analysis of TRAMP prostate lesions revealed greatly elevated Dnmt1 mRNA and protein levels beginning in prostatic intraepithelial neoplasia and continuing through advanced prostate cancer and metastasis. Interestingly, when TRAMP mice were treated in a chemopreventive manner with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza), 0 of 14 mice developed prostate cancer at 24 weeks of age, whereas 7 of 13 (54%) control-treated mice developed poorly differentiated prostate cancer. Treatment with 5-aza also prevented the development of lymph node metastases and dramatically extended survival compared with control-treated mice. Taken together, these data suggest that Dnmt1 is rapidly activated by pRb pathway inactivation, and that DNA methyltransferase activity is required for malignant transformation and tumorigenesis. PMID: 16397253 [PubMed - indexed for MEDLINE]
February 20, 2006
Under pressure: stromal fibroblasts change their ways.
Under pressure: stromal fibroblasts change their ways.
Under pressure: stromal fibroblasts change their ways. Cell. 2005 Dec 16;123(6):985-7 Authors: Bierie B, Moses HL In this issue of Cell, Hill et al. (2005) demonstrate in a mouse model of prostate cancer that the tumor cells can initiate and promote expansion of stromal fibroblasts that lack the tumor-suppressor protein p53 through a paracrine mechanism. This results in selection of highly proliferative fibroblasts associated with the carcinoma that further promote tumor progression. PMID: 16360028 [PubMed - indexed for MEDLINE]
February 15, 2006
Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.
Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.
Related Articles Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer. Clin Cancer Res. 2005 Oct 15;11(20):7523-31 Authors: Ryo A, Uemura H, Ishiguro H, Saitoh T, Yamaguchi A, Perrem K, Kubota Y, Lu KP, Aoki I PURPOSE: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer. EXPERIMENTAL DESIGN: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. RESULTS: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis. CONCLUSIONS: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors. PMID: 16243827 [PubMed - indexed for MEDLINE]
February 14, 2006
[Expression of Trp-p8 in prostate and its significant]
[Expression of Trp-p8 in prostate and its significant]
Related Articles [Expression of Trp-p8 in prostate and its significant] Zhonghua Yi Xue Za Zhi. 2005 Jun 15;85(22):1571-3 Authors: Wang HP, Yang XR, Wang XH, Ma SL PMID: 16179122 [PubMed - indexed for MEDLINE]
[Expression of Trp-p8 in prostate and its significant]
[Expression of Trp-p8 in prostate and its significant]
Related Articles [Expression of Trp-p8 in prostate and its significant] Zhonghua Yi Xue Za Zhi. 2005 Jun 15;85(22):1571-3 Authors: Wang HP, Yang XR, Wang XH, Ma SL PMID: 16179122 [PubMed - indexed for MEDLINE]
February 13, 2006
E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.
E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer.
Related Articles E-cadherin gene 3'-UTR C/T polymorphism is associated with prostate cancer. Urol Int. 2005;75(4):350-3 Authors: Wu HC, Lai MT, Wu CI, Chen HY, Wan L, Tsai FJ, Chen WC INTRODUCTION: E-cadherin (CDH-1) is a cell-cell adhesive molecule which maintains cell integrity and communication between the intracellular and extracellular world. CDH-1 may therefore be related to carcinogenesis. A polymorphism located at the 3'-UTR of the CDH-1 gene is associated with stone disease; however, its relationship to prostate cancer has not been reported. We aimed to study whether there is an association between the 3'-UTR polymorphism and prostate cancer. MATERIALS AND METHODS: We collected 96 patients with prostate cancer and 114 normal controls for this study. The polymorphism of the CDH-1 gene was studied by polymerase chain reaction-based restriction analysis. RESULTS: There was a significant difference in genotype distribution of the CDH-1 gene polymorphism between cancer patients and normal controls (p < 0.001). The distribution of the CDH-1 gene CC genotype in prostate cancer patients (51.0%) was higher than in the controls (10.5%). The odds ratio for the CDH-1 'C' allele was 2.896 (95% CI = 1.908-4.396). There was no significant difference according to age, pathological grading, clinical staging, and responsiveness to hormonal therapy among patients. Only 3 patients (3.1%) had a history of urolithiasis. CONCLUSIONS: The CDH-1 gene 3'-UTR C/T polymorphism is associated with prostate cancer. The 'CC' homozygote indicates a relatively higher risk for developing prostate cancer than other genotypes. PMID: 16327305 [PubMed - indexed for MEDLINE]
A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.
A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers.
Related Articles A novel cancer testis antigen that is frequently expressed in pancreatic, lung, and endometrial cancers. Clin Cancer Res. 2006 Jan 1;12(1):191-7 Authors: Okada T, Akada M, Fujita T, Iwata T, Goto Y, Kido K, Okada T, Matsuzaki Y, Kobayashi K, Matsuno S, Sunamura M, Kawakami Y PURPOSE: To isolate cancer testis antigens that are expressed in pancreatic cancers and may be useful in clinical applications. EXPERIMENTAL DESIGN: To efficiently isolate cancer testis antigens, a testis cDNA library was immunoscreened (SEREX) with serum from a patient with pancreatic ductal adenocarcinoma. The expression of isolated antigens in various cancer cell lines and tissues was evaluated by reverse transcription-PCR and Northern blot analyses. The immunogenicity of the antigen in cancer patients was evaluated by detection of the IgG antibody in sera from patients with various cancers. RESULTS: Of the three clones isolated through screening of a total of 2 x 10(6) cDNA library clones, one clone (KU-CT-1) was found to be expressed in various cancers but only in testis among normal tissues, indicating that it was a novel cancer testis antigen. The KU-CT-1 gene is located on chromosome 10p12 and produces two splice variants, which encode proteins of 397 and 872 amino acids, respectively. KU-CT-1 was expressed in pancreatic cancer tissues (3 of 9, 33%), lung cancer tissues (9 of 24, 38%), and endometrial cancer tissues (7 of 11, 64%). Specific serum IgG antibodies were detected in 3 of 20 pancreatic cancer patients, 2 of 12 endometrial cancer patients, 1 of 18 colon cancer patients, and 1 of 10 prostate cancer patients but not detected in 30 healthy individuals. CONCLUSIONS: KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers and may be useful for diagnosis and immunotherapy for patients with various cancers. PMID: 16397042 [PubMed - indexed for MEDLINE]
February 12, 2006
Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells.
Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells.
Related Articles Tightly-regulated suicide gene expression kills PSA-expressing prostate tumor cells. Gene Ther. 2005 Nov;12(21):1573-80 Authors: Peng W, Chen J, Huang YH, Sawicki JA We have previously shown that a dual system for controlling gene expression that relies both on transcriptional regulation and DNA recombination mediated by the site-directed recombinase, Flp, effectively controls the expression of a gene encoding diphtheria toxin (DT-A). In this study, we investigated the use of a chimeric modified enhancer/promoter sequence of the human prostate-specific antigen (PSA) gene to regulate DT-A expression in human prostate cancer cells in culture, in xenografts derived from these cells, and in autochthonous tumors in TRAMP mice. Following adenoviral delivery of DNA encoding PSA promoter-driven Flp recombinase and DT-A, we demonstrate that this transcriptional/DNA recombination control strategy effectively activates DT-A expression in a manner that correlates with the amount of PSA and androgen in cells. Significantly, the size of xenografts was reduced by 50%, and tumor cells in TRAMP mice died following intratumoral injection of DT-A viruses. Direct injection of virally-delivered DT-A into normal mouse prostates resulted in a dramatic reduction in the size of the gland. Our results suggest that the PSA promoter-driven Flp recombinase regulatory system will allow for targeted death of PSA-expressing cells. When combined with newly developed strategies for targeted gene delivery, this approach holds promise as an effective systemically-administered therapy for metastatic prostate cancer. PMID: 16034457 [PubMed - indexed for MEDLINE]
February 9, 2006
Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination.
Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination.
Related Articles Optimizing prostate cancer treatment by combining local radiation therapy with systemic vaccination. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6757-62 Authors: Kaufman HL, Divgi CR PMID: 16203760 [PubMed - indexed for MEDLINE]
February 8, 2006
Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells.
Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells.
Related Articles Human Kruppel-like factor 5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells. J Biol Chem. 2005 Dec 16;280(50):41553-61 Authors: Chen C, Sun X, Guo P, Dong XY, Sethi P, Cheng X, Zhou J, Ling J, Simons JW, Lingrel JB, Dong JT The transcription factor KLF5 plays an important role in human carcinogenesis. In epithelial cells, the KLF5 protein is tightly regulated by the ubiquitin-proteasome pathway. To better understand the mechanisms for the regulation of KLF5 protein, we identified and characterized an E3 ubiquitin ligase for KLF5, i.e. WWP1. We found that WWP1 formed a protein complex with KLF5 in vivo and in vitro. Furthermore, WWP1 mediated the ubiquitination and degradation of KLF5, and the catalytic cysteine residue of WWP1 is essential for its function. A PY motif in a transactivation domain of KLF5 is necessary for its interaction with WWP1. Finally, WWP1 was amplified and overexpressed in some cancer cell lines from the prostate and breast, which negatively regulated the function of KLF5 in gene regulation. These findings not only established WWP1 as an E3 ubiquitin ligase for KLF5, they also further implicated the KLF5 pathway in human carcinogenesis. PMID: 16223724 [PubMed - indexed for MEDLINE]
February 7, 2006
A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.
A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis.
Related Articles A cancer DNA phenotype in healthy prostates, conserved in tumors and adjacent normal cells, implies a relationship to carcinogenesis. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19093-6 Authors: Malins DC, Gilman NK, Green VM, Wheeler TM, Barker EA, Anderson KM A cancer DNA phenotype, identical to the DNA structure of tumors, has been identified in the prostate glands of certain healthy men over 55 years of age. We now show that the same DNA signature exists in normal tissues adjacent to tumors. This finding implies that the phenotype is maintained in normal prostate cells from its inception through tumor development. The presence of the phenotype in tumors, adjacent normal cells, and in the normal prostate cells of certain older men suggests that it is a potentially critical factor in tumor development and may serve as an early biomarker for cancer risk assessment. Intervention to inhibit the development of the phenotype in healthy men, or to eliminate it once formed, may suppress or even prevent tumor formation. PMID: 16361440 [PubMed - indexed for MEDLINE]
February 5, 2006
Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator.
Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator.
Related Articles Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator. Biochemistry. 2005 Dec 6;44(48):15664-73 Authors: Dalal S, Hile S, Eckert KA, Sun KW, Starcevic D, Sweasy JB Studies show that 30% of 189 tumors sequenced to date express variants of the polymerase beta (pol beta) protein that are not present in normal tissue. This raises the possibility that variants of pol beta might be linked to the etiology of cancer. Here, we characterize the I260M prostate-cancer-associated variant of pol beta. Ile260 is a key residue of the hydrophobic hinge that is important for the closing of the polymerase. In this study, we demonstrate that the I260M variant is a sequence context-dependent mutator polymerase. Specifically, I260M is a mutator for misalignment-mediated errors in dipyrimidine sequences. I260M is also a low-fidelity polymerase with regard to the induction of transversions within specific sequence contexts. Our results suggest that the hinge influences the geometry of the DNA within the polymerase active site that is important for accurate DNA synthesis. Importantly, characterization of the I260M variant shows that it has a functional phenotype that could be linked to the etiology or malignant progression of human cancer. PMID: 16313169 [PubMed - indexed for MEDLINE]
January 30, 2006
Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells.
Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells.
Related Articles Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncol. 2005 Aug;76(2):168-76 Authors: Meng AX, Jalali F, Cuddihy A, Chan N, Bindra RS, Glazer PM, Bristow RG BACKGROUND AND PURPOSE: Intratumoral hypoxia has been correlated with poor clinical outcome in prostate cancer. Prostate cancer cells can be genetically unstable and have altered DNA repair. We, therefore, hypothesized that the expression of DNA double-strand break (DNA-dsb) repair genes in normal and malignant prostate cultures can be altered under hypoxic conditions. METHODS AND MATERIALS: The expression of homologous recombination (HR) and non-homologous recombination (NHEJ) genes following gas hypoxia (0.2%) or exposure to HIF1alpha-inducing agent, CoCl2 (100 microM), was determined for normal diploid fibroblasts (GM05757) and the pre-malignant and malignant prostate cell lines, BPH-1, 22RV-1, DU145 and PC3. RNA and protein levels were determined using RT-PCR and Western blotting. Additionally, p53 genotype and function, the level of hypoxia-induced apoptosis, and cell cycle distribution, were determined to correlate to changes in DNA-dsb gene expression. RESULTS: Induction of hypoxia was confirmed using HIF1alpha and VEGF expression in gas- and CoCl2-treated cultures. Hypoxia (48-72 h of 0.2% O2) decreased RNA expression of a number of HR-related genes (e.g. Rad51, Rad52, Rad54, BRCA1, BRCA2) in both normal and malignant cultures. Similar decreases in RNA pertaining to the NHEJ-related genes (e.g. Ku70, DNA-PKcs, DNA Ligase IV, Xrcc4) were observed. In selected cases, hypoxia-mediated decreases in RNA expression led to decreased DNA-dsb protein expression. CoCl2-treated cultures did not show decreased DNA-dsb protein expression. The ability of hypoxia to down-regulate Rad51 and other HR-associated genes under hypoxia was not correlated to c-Abl or c-Myc gene expression, p53 genotype or function, propensity for hypoxia-mediated apoptosis, or specific changes in cell cycle distribution. CONCLUSIONS: Hypoxia can down-regulate expression of DNA-dsb repair genes in both normal and cancer cells. If associated with a functional decrease in DNA-dsb repair, this observation could provide a potential basis for the observed genetic instability within tumor cells exposed to hypoxia. PMID: 16026872 [PubMed - indexed for MEDLINE]
January 29, 2006
Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines.
Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines.
Related Articles Biochemical nature and mapping of PSMA epitopes recognized by human antibodies induced after immunization with gene-based vaccines. Anticancer Res. 2005 Nov-Dec;25(6C):4727-32 Authors: Todorova K, Zoubak S, Mincheff M, Kyurkchiev S BACKGROUND: A possible new target for immunotherapy is the prostate-specific membrane antigen (PSMA). The aim of the present study was to define potential PSMA epitopes for antibody binding using sera from patients immunized with gene-based anti-PSMA vaccines. MATERIALS AND METHODS: Sera from prostate cancer patients, immunized repeatedly with plasmid and adenoviral vectors, each encoding for the extracellular portion of human PSMA, were tested for anti-PSMA antibodies by Western blot. PSMA-producing LNCaP cells were used as a control. Recombinant PSMA protein cleaved with different proteinases was used for epitope mapping. Different enzymes were used to cleave the PSMA molecule. RESULTS: Specific anti-PSMA antibodies were detected in the studied patients' sera, mainly against the PSMA protein core. An alignment of the predicted enzyme-cleavage fragments was compared with Western blot results and several antibody epitopes were determined. CONCLUSION: These data demonstrate that multiple gene-based vaccinations induce an anti-PSMA humoral immune response. The antibodies are predominantly specific for the PSMA protein core. PMID: 16334167 [PubMed - indexed for MEDLINE]
January 28, 2006
Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis.
Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis.
Related Articles Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis. Int J Oncol. 2006 Jan;28(1):217-29 Authors: Skjøth IH, Issinger OG We have treated four prostate tumor cell lines, DU-145, PC-3, LNCaP and 22RV1 with various concentrations of cisplatin in order to check for influence on viability and for onset of apoptosis induction. At a cisplatin concentration of 20 microM, 22RV1 and DU-145 cells showed approximately 22% and 18% and PC-3 and LNCaP cells showed approximately 4 and 10% dead cells, respectively. When checking for apoptosis induction, the differences among the cell lines became even more evident. DU-145 and 22RV1 cells showed apoptosis induction at 5- and 2-microM cisplatin, whereas in the case of LNCaP and PC-3 cells comparable apoptosis induction was observed at 100-microM cisplatin; hence, the difference between the two groups of cell lines with respect to apoptosis induction is 20- and 50-fold, respectively. We used 37 antibodies to screen the expression levels of key signaling molecules and their phosphorylation status where appropriate. DU-145 and PC-3 cells are androgen-receptor negative and harbor non-functional p53, whereas LNCaP and 22RV1 cells are androgen-receptor positive and harbor wild-type p53. The results of the profiling of DU-145 and PC-3 support the notion that an intact PTEN/AKT pathway (as found in DU-145 and 22RV1 cells) and the presence of active p38 are responsible for the high sensitivity to apoptosis induction and that neither the androgen receptor nor the p53 status is of primary importance for the differences observed with respect to apoptosis induction. PMID: 16327999 [PubMed - indexed for MEDLINE]
January 24, 2006
Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer.
Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer.
Related Articles Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer. Int J Cancer. 2005 Dec 10;117(5):738-45 Authors: Rauhala HE, Porkka KP, Tolonen TT, Martikainen PM, Tammela TL, Visakorpi T Inactivation of tumor suppressor genes through deletion, mutation and epigenetic silencing has been shown to occur in cancer. In our study, we combined DNA demethylation and histone deacetylation inhibition treatments with suppression subtraction hybridization (SSH) and cDNA microarrays to identify potentially epigenetically downregulated genes in PC-3 prostate cancer cell line. We found 11 genes whose expression was upregulated after relieving epigenetic regulation. Expression of 3 genes [dual-specificity phosphatase 1 (DUSP1), serum/glucocorticoid regulated kinase (SGK) and spermidine/spermine N1-acetyltransferase (SAT)] was subsequently studied in clinical sample material using real-time quantitative RT-PCR and immunohistochemistry. The DUSP1 and SGK mRNA expression was lower in hormone-refractory prostate carcinomas compared to benign prostate hyperplasia (BPH) or untreated prostate carcinomas. BPH, normal prostate and high-grade prostate intraepithelial neoplasia (PIN) expressed high levels of DUSP1 and SGK proteins. Ninety-two percent and 48% of the prostate carcinomas showed almost complete lack of DUSP1 and SGK proteins, respectively, indicating common downregulation of these genes. The genomic bisulphite sequencing did not reveal dense hypermethylation in the promoter regions of either DUSP1 or SGK. In conclusion, the data suggest that downregulation of DUSP1 and SGK is an early event and could be important in the tumorigenesis of prostate cancer. PMID: 15981206 [PubMed - indexed for MEDLINE]
January 23, 2006
Polo-like kinase (Plk) 1 as a target for prostate cancer management.
Polo-like kinase (Plk) 1 as a target for prostate cancer management.
Related Articles Polo-like kinase (Plk) 1 as a target for prostate cancer management. IUBMB Life. 2005 Oct;57(10):677-82 Authors: Reagan-Shaw S, Ahmad N Prostate cancer (PCa) is the most commonly occurring cancer in American men, next to skin cancer. Existing treatment options and surgical intervention are unable to effectively manage this cancer. Therefore, continuing efforts are ongoing to establish novel mechanism-based targets and strategies for its management. The serine/threonine kinases Polo-like kinase (Plk) 1 plays a key role in mitotic entry of proliferating cells and regulates many aspects of mitosis which are necessary for successful cytokinesis. Plk1 is over-expressed in many tumor types with aberrant elevation frequently constituting a prognostic indicator of poor disease outcome. This review discusses the studies which indicate that Plk1 could be an excellent target for the treatment as well as chemoprevention of prostate cancer. PMID: 16223707 [PubMed - indexed for MEDLINE]
January 21, 2006
Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells.
Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells.
Related Articles Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells. Biol Cell. 2005 Dec;97(12):893-903 Authors: Miekus K, Czernik M, Sroka J, Czyz J, Madeja Z BACKGROUND INFORMATION: Motile activity of tumour cells is regarded as a critical factor determining their metastatic potential. We have shown previously that contrary to the majority of normal cells, homotypic contacts between some tumour cells, among them low metastatic (AT-2) and highly metastatic (MAT-LyLu) rat prostate cancer cells, increase the speed of their movements. The aim of the present study was to determine the effect of heterotypic cell-to-cell contacts on the migration of rat prostate cancer cells differing in metastatic potential, and to correlate it with the intensity of homo- and heterologous gap junctional coupling. RESULTS: MAT-LyLu and AT-2 cells moving on the surface of fibroblasts displayed significantly greater cell displacement than those moving on plastic substrata. This effect correlated with the polarization (contact guidance) and increased speed of cell movements. However, in contrast with the migration on plastic substrata, where MAT-LyLu cells displayed considerably higher motility than AT-2 cells, no differences between both cell lines were observed on the surface of fibroblasts. On the other hand, in contrast with AT-2, Mat-LyLu cells displayed extensive homologous coupling mediated by connexin43 and were able to couple with normal fibroblasts. CONCLUSION: Heterotypic contacts between migrating prostatic cancer cells and normal fibroblasts can strongly stimulate their migration during invasion; however, this effect does not correlate with the gap junctional coupling between cancer cells and normal fibroblasts. PMID: 15907197 [PubMed - indexed for MEDLINE]
January 18, 2006
Identification of a positive Cis-element upstream of human NKX3.1 gene.
Identification of a positive Cis-element upstream of human NKX3.1 gene.
Related Articles Identification of a positive Cis-element upstream of human NKX3.1 gene. Acta Biochim Biophys Sin (Shanghai). 2005 Nov;37(11):773-8 Authors: Jiang AL, Zhang PJ, Hu XY, Chen WW, Kong F, Liu ZF, Yuan HQ, Zhang JY NKX3.1 is a prostate-specific homeobox gene related to prostate development and prostate cancer. In this work, we aimed to identify precisely the functional cis-element in the 197 bp region (from -1032 to -836 bp) of the NKX3.1 promoter (from -1032 to +8 bp), which was previously identified to present positive regulatory activity on NKX3.1 expression, by deletion mutagenesis analysis and electrophoretic mobility shift assay (EMSA). A 16 bp positive cis-element located between -920 and -905 bp upstream of the NKX3.1 gene was identified by deletion mutation analysis and proved to be a functional positive cis-element by EMSA. It will be important to further study the functions and regulatory mechanisms of this positive cis-element in NKX3.1 gene expression. PMID: 16270157 [PubMed - indexed for MEDLINE]
January 13, 2006
The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.
The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.
Related Articles The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2563-8 Authors: Xu J, Lowey J, Wiklund F, Sun J, Lindmark F, Hsu FC, Dimitrov L, Chang B, Turner AR, Liu W, Adami HO, Suh E, Moore JH, Zheng SL, Isaacs WB, Trent JM, Gr nberg H It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field. PMID: 16284379 [PubMed - indexed for MEDLINE]
January 12, 2006
[Advances on inhibin genes.]
[Advances on inhibin genes.]
Related Articles [Advances on inhibin genes.] Yi Chuan. 2004 Sep;26(5):749-55 Authors: Xue Y, Chu MX, Zhou ZX Inhibins are gonadal glycoprotein hormones belonging to the transforming growth factor-beta superfamily that act to suppress pituitary follicle-stimulating hormone synthesis and secretion. In this paper, we briefly introduced the cloning, structure, localization, polymorphism, expression, molecular regulation of inhibin-alpha(INHA), -betaA (INHBA) and -beta B (INHBB) subunit genes and their relationships with reproductive performance and cancer. The inhibin genes (INHA, INHBA and INHBB) had significant effect on litter size in sheep. The ovine INHA, INHBA and INHBB genes had been mapped to chromosomes 2q41-->q43, 4q26 and 2q31-->q33, respectively. The female mice carrying INHBB mutations suffered from distinct developmental and reproductive defects. The INHA gene was significantly associated with premature ovarian failure in women. PMID: 15640097 [PubMed - indexed for MEDLINE]
January 11, 2006
Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers.
Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers.
Related Articles Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers. Mol Cancer Ther. 2005 Jul;4(7):1047-55 Authors: Dong Y, Zhang H, Gao AC, Marshall JR, Ip C Our previous report showed that methylseleninic acid (MSA) significantly decreases the expression of androgen receptor and prostate-specific antigen (PSA) in LNCaP cells. The present study extended the above observations by showing the universality of this phenomenon and that the inhibitory effect of MSA on prostate cancer cell growth and cancer-specific biomarkers is mediated through androgen receptor down-regulation. First, MSA decreases the expression of androgen receptor and PSA in five human prostate cancer cell lines (LNCaP, LAPC-4, CWR22Rv1, LNCaP-C81, and LNCaP-LN3), irrespective of their androgen receptor genotype (wild type versus mutant) or sensitivity to androgen-stimulated growth. Second, by using the ARE-luciferase reporter gene assay, we found that MSA suppression of androgen receptor transactivation is accounted for primarily by the reduction of androgen receptor protein level. Third, MSA inhibition of five androgen receptor-regulated genes implicated in prostate carcinogenesis (PSA, KLK2, ABCC4, DHCR24, and GUCY1A3) is significantly attenuated by androgen receptor overexpression. Fourth, transfection of androgen receptor in LNCaP cells weakened noticeably the inhibitory effect of MSA on cell growth and proliferation. Androgen receptor signaling has been documented extensively to play an important role in the development of both androgen-dependent and -independent prostate cancer. Our finding that MSA reduces androgen receptor availability by blocking androgen receptor transcription provides justification for a mechanism-driven intervention strategy in using selenium to control prostate cancer progression. PMID: 16020662 [PubMed - indexed for MEDLINE]
January 7, 2006
(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals.
(99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals.
Related Articles (99m)Tc-EC-guanine: synthesis, biodistribution, and tumor imaging in animals. Pharm Res. 2005 Sep;22(9):1471-9 Authors: Yang DJ, Ozaki K, Oh CS, Azhdarinia A, Yang T, Ito M, Greenwell A, Bryant J, Kohanim S, Wong VK, Kim EE PURPOSE: DNA markers are useful in assessing cell proliferation. The purpose of this study was to synthesize (99m)Tc-ethylenedicysteine-guanine (EC-Guan) for evaluation of cell proliferation. METHODS: Tumor cells were incubated with (99m)Tc-EC-Guan for cell cycle analysis. Prostate tumor cells that were overexpressing the HSV thymidine kinase gene, or various tumor cells were incubated with (99m)Tc-EC-Guan at 0.5-2 h. Thymidine incorporation assays were performed in lung cancer cells incubated with EC-Guan at 0.1-1 mg/well. Tissue distribution, autoradiography, and planar scintigraphy of (99m)Tc-EC-Guan and (99m)Tc-EC (control) were determined in tumor-bearing rodents at 0.5-4 h. RESULTS: Cell culture assays indicated that EC-Guan was incorporated in DNA, and there was no significant uptake difference between HSVTK overexpressed and normal groups. Biodistribution and scintigraphic imaging studies of (99m)Tc-EC-Guan showed increased tumor/tissue count density ratios as a function of time. CONCLUSIONS: Our results indicate that (99m)Tc-EC-Guan may be useful as a tumor proliferation imaging agent. PMID: 16132359 [PubMed - indexed for MEDLINE]