Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mutations of BRCA1 and p53 genes have been simultaneously characterized in many tumors. However, their coexpression and associations have not been investigated quantitatively in prostate cancer. In the present study, the expressions of the mutated BRCA1 mRNA and p53 mRNA were examined in 48 Chinese prostate cancer cases and 10 corresponding adjacent benign tissues with in situ hybridization. The 5-year survival rates of the corresponding patients after operation were investigated. The results showed that the positive expressions of the mutated BCRA1 mRNA and p53 mRNA are involved in prostate cancer (P < 0.05). Moreover, there is a closed negative association between the expressions of the mutated BRCA1 gene and p53 gene in the mRNA level with the progression, angiogenesis, metastasis, and survival rate of prostate cancer. Their coexpression and negative association suggest that the two altered tumor suppressor genes might interact functionally in prostate cancer to provide a potential signal determining a prognosis of the tumor metastasis and survival rate. Further work will be done to elucidate the interaction mechanisms in prostate cancer.
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PMID:Coexpression of the mutated BRCA1 mRNA and p53 mRNA and its association in Chinese prostate cancer. 1926 98

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in the United States. CpG island methylation causes gene silencing and could be decisive in prostate carcinogenesis and progression. Its role was investigated at multiple gene sites during prostate carcinogenesis. Methylation-specific polymerase chain reaction (MS-PCR) was used to analyze 4 interest gene promoter status in 12 patients with adenocarcinoma, 7 patients with prostate intraepithelial neoplasia, 3 patients with peritumor tissues and 15 healthy patients, so a total of 37 prostate biopsy samples constituted the cohort of the study. Despite the biopsy histology, the results have confirmed that BRCA1, RASSF1, GSTP1 and EPHB2 promoter methylation was found in each sample, except two.
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PMID:Methylation analysis of BRCA1, RASSF1, GSTP1 and EPHB2 promoters in prostate biopsies according to different degrees of malignancy. 1945 3

The hormonal-regulated serpin, ovine uterine serpin (OvUS), also called uterine milk protein (UTMP), inhibits proliferation of lymphocytes and prostate cancer (PC-3) cells by blocking cell-cycle progression. The present aim was to identify cell-cycle-related genes regulated by OvUS in PC-3 cells using the quantitative human cell-cycle RT(2) Profiler PCR array. Cells were cultured +/-200 microg/ml recombinant OvUS (rOvUS) for 12 and 24 h. At 12 h, rOvUS increased expression of three genes related to cell-cycle checkpoints and arrest (CDKN1A, CDKN2B, and CCNG2). Also, 14 genes were down-regulated including genes involved in progression through S (MCM3, MCM5, PCNA), M (CDC2, CKS2, CCNH, BIRC5, MAD2L1, MAD2L2), G(1) (CDK4, CUL1, CDKN3) and DNA damage checkpoint and repair genes RAD1 and RBPP8. At 24 h, rOvUS decreased expression of 16 genes related to regulation and progression through M (BIRC5, CCNB1, CKS2, CDK5RAP1, CDC20, E2F4, MAD2L2) and G(1) (CDK4, CDKN3, TFDP2), DNA damage checkpoints and repair (RAD17, BRCA1, BCCIP, KPNA2, RAD1). Also, rOvUS down-regulated the cell proliferation marker gene MKI67, which is absent in cells at G(0). Results showed that OvUS blocks cell-cycle progression through upregulation of cell-cycle checkpoint and arrest genes and down-regulation of genes involved in cell-cycle progression.
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PMID:Changes in expression of cell-cycle-related genes in PC-3 prostate cancer cells caused by ovine uterine serpin. 1953 Feb 25

Men who carry mutations in BRCA1 or BRCA2 are at increased risk for prostate cancer. However the efficacy of prostate screening in this setting is uncertain and limited data exists on the uptake of prostate screening by mutation carriers. This study prospectively evaluated uptake of prostate cancer screening in a multi-institutional cohort of mutation carriers. Subjects were unaffected male BRCA1 and BRCA2 mutation carriers, aged 40-69 years, enrolled in the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) and who had completed a mailed, self-report follow-up questionnaire 3 yearly after study entry. Of the 75 male carriers in this study, only 26 (35%) had elected to receive their mutation result. Overall, 51 (68%) did not recall having received a recommendation to have prostate screening because of their family history, but 41 (55%) had undergone a prostate specific antigen (PSA) test and 32 (43%) a digital rectal examination (DRE) in the previous 3 years. Those who were aware of their mutation result were more likely to have received a recommendation for prostate screening (43 vs. 6%, p = 0.0001), and to have had a PSA test (77 vs. 43%, p = 0.005) and a DRE (69 vs. 29%, p = 0.001) in the previous 3 years. The majority of unaffected males enrolled in kConFab with a BRCA1/2 mutation have not sought out their mutation result. However, of those aware of their positive mutation status, most have undergone at least one round of prostate screening in the previous 3 years.
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PMID:Prostate screening uptake in Australian BRCA1 and BRCA2 carriers. 1972 93

Epidemiologic research conducted over the last two decades has led us to believe that inherited factors play an important role in the aetiology of prostate cancer, but the genes which underlie the inherited susceptibility are elusive. The most compelling associations to date are with genes involved in DNA damage repair, including BRCA2. In Poland we have initiated a programme to identify DNA variants which confer an increased risk of prostate cancer and other cancers. Here we review our recent results. We found that germline mutations in BRCA1, CHEK2 and NBS1 confer an increased prostate cancer risk in Polish men. We provide evidence that CHEK2 is a multi-organ cancer susceptibility gene. We show that inherited variation in RNASEL and MSR1 genes do not contribute to prostate cancer development in Poland.
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PMID:Selected aspects of inherited susceptibility to prostate cancer and tumours of different site of origin. 1972 94

BRCA1, a tumor suppressor, participates in DNA damage signaling and repair. Previously, we showed that BRCA1 overexpression caused inhibition of telomerase activity and telomere shortening in breast and prostate cancer cells. We now report that BRCA1 knockdown causes increased telomerase reverse transcriptase expression, telomerase activity, and telomere length; but studies utilizing a combination of BRCA1 and telomerase reverse transcriptase small interfering RNAs suggest that BRCA1 also regulates telomere length independently of telomerase. Using telomeric chromatin immunoprecipitation assays, we detected BRCA1 at the telomere and demonstrated time-dependent loss of BRCA1 from the telomere following DNA damage. Further studies suggest that BRCA1 interacts with TRF1 and TRF2 in a DNA-dependent manner and that some of the nuclear BRCA1 colocalizes with TRF1/2. Our findings further suggest that Rad50 is required to localize BRCA1 at the telomere and that the association of BRCA1 with Rad50 does not require DNA. Finally, we found that BRCA1 regulates the length of the 3' G-rich overhang in a manner that is dependent upon Rad50. Our findings suggest that BRCA1 is recruited to the telomere in a Rad50-dependent manner and that BRCA1 may regulate telomere length and stability, in part through its presence at the telomere.
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PMID:BRCA1 localization to the telomere and its loss from the telomere in response to DNA damage. 1979 51

Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more aggressive than morphologically similar cancers in men without these mutations. This study was performed to test the hypothesis that enhanced expression of Ki-67, as a surrogate of cell proliferation, is a characteristic feature of prostate cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised 20 cases of prostate cancer in mutation carriers and 126 control sporadic prostate cancers. Of the combined sample cohort, 65.7% stained only within malignant tissues while 0.7% stained in both malignant and benign tissues (p<0.001). Significantly increased expression of Ki-67 occurred in prostate cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in 67% of the sporadic controls (p>0.5). Similar results were obtained when the data were analysed using a threshold set at 3.5 and 7.1%. This study shows that elevated expression of Ki-67 is associated both with aggressive prostate cancers and with high Gleason score irrespective of whether their occurrence is against a background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest that, since elevated Ki-67 does not distinguish prostate cancers occurring in BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the effects of these genetic mutations are probably independent. While all prostate cancers occurring in the presence of BRCA germline mutations are clinically aggressive, their potentially different phenotypes consistently involve maximal rates of cell proliferation.
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PMID:Elevated expression of Ki-67 identifies aggressive prostate cancers but does not distinguish BRCA1 or BRCA2 mutation carriers. 2004 88

Prediction of cancer progression after radical prostatectomy is one of the most challenging problems in the management of prostate cancer. Gene-expression profiling is widely used to identify genes associated with such progression. Usually candidate genes are identified according to a gene-by-gene comparison of expression. Recent reports suggested that relative expression of a gene pair more efficiently predicts cancer progression than single-gene analysis does. The top-scoring pair (TSP) algorithm classifies phenotypes according to the relative expression of a pair of genes. We applied the TSP approach to predict, which patients would experience systemic tumor progression after radical prostatectomy. Relative expression of TPD52L2/SQLE and CEACAM1/BRCA1 gene pairs identified those patients with more than 99% specificity but relatively low sensitivity (approximately 10%). These two gene pairs were validated in three independent data sets. In addition, combining two pairs of genes improved sensitivity without compromising specificity. Functional annotation of the TSP genes showed that they cluster by a limited number of biological functions and pathways, suggesting that relatively lower expression of genes from specific pathways can predict cancer progression. In conclusion, comparative analysis of the expression of two genes may be a simple and effective classifier for prediction of prostate cancer progression. In summary, the TSP approach can be used to identify patients whose prostate cancer will progress after they undergo radical prostatectomy. Two gene pairs can predict which men would experience progression to the metastatic form of the disease. However, because our analysis was based on a relatively small number of genes, a larger study will be needed to identify the best predictors of disease outcome overall.
Prostate Cancer Prostatic Dis 2010 Sep
PMID:Usefulness of the top-scoring pairs of genes for prediction of prostate cancer progression. 2038 65

BRCA1 functions as a tumor suppressor; recent work suggests that BRCA1 may also induce cell cycle arrest to allow for DNA repair. We hypothesized that BRCA1 expression in prostate tumor tissue may be associated with prostate cancer progression through regulation of the cell cycle. We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from 393 prostate cancer cases in the Physicians' Health Study. The men were followed prospectively from diagnosis to development of metastases and mortality. Fifteen percent of tumors stained positive for BRCA1. BRCA1-positive tumors had substantially increased tumor proliferation index compared with negative tumors (47.0 Ki67-positive nuclei versus 10.3, P = 0.0016) and were more likely to develop lethal cancer compared with BRCA1-negative tumors (hazard ratio, 4.6; 95% confidence interval, 2.4-8.7). These findings strengthen the hypothesis that BRCA1 plays a role in cell cycle control and show that BRCA1 is a marker of clinical prostate cancer prognosis. Cancer Res; 70(8); 3136-9. (c)2010 AACR.
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PMID:Immunohistochemical expression of BRCA1 and lethal prostate cancer. 2038 72

Extract: A single inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight into the genetic basis of carcinogenesis, but they are relatively rare and account for only a small fraction of all cancers. Examples include mutation to the APC gene, causing early onset colon cancer in the syndrome familial adenomatous polyposis (tumorous polyp-tissue in the colon); mutation to either the BRCA1 or BRCA2 genes, causing an increased risk of breast cancer; and mutation to the TP53 gene, causing Li-Fraumeni syndrome with various early onset cancers such as bone or soft tissue sarcoma. Cancers sometimes cluster in families, but do not follow the rigid inheritance pattern characteristic of a mutation to a single gene. Males with a brother or father who has suffered prostate cancer are more likely to develop the disease. Similarly, females with a sister or mother who has suffered breast cancer are more likely to get a breast tumor. Some of the clustering may arise from the common diet and environment shared by families. Recently, however, researchers have begun to assign a significant fraction of cancer risk to the particular genetic variants that individuals inherit.
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PMID:Inheritance of cancer. 2070 38


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