We stably expressed wild-type (wt) and tumor-associated mutant BRCA1 transgenes in DU-145, a human prostate cancer cell line with low endogenous expression of BRCA1.
In summary, these results show that the activation of BRCA1-NRF2/HO-1 axis defines a new mechanism for the maintenance of the cellular homeostasis in prostate cancer.
We previously reported that expression of the breast cancer susceptibility gene BRCA1 strongly inhibits the transcriptional activity of the estrogen receptor (ER-alpha) in human breast and prostate cancer cell lines but only weakly inhibits ER-alpha activity in cervical cancer cells (S. Fan et al., Science (Wash. DC), 284: 1354-1356, 1999).
In addition, an inverse correlation between BRCA1 and IGF-IR levels was observed in the androgen receptor (AR)-negative prostate cancer-derived P69 and M12 cell lines.
Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers.
The BRCA1 gene was previously found to inhibit the transcriptional activity of the estrogen receptor [ER-alpha] in human breast and prostate cancer cell lines.
Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers.
We report 8 additional genes with suggestive evidence of association, including the DNA repair genes PARP2 and MSH6 Finally, we observed an excess of rare truncation variants in 5 genes, including the DNA repair genes MSH6, BRCA1, and BRCA2 This adds to the growing body of evidence that DNA repair pathway defects may influence susceptibility to aggressive prostate cancer.
The purpose of this article is to provide a review of principles of genetic testing in prostate cancer and highlight the significance of clinical genetic testing of BRCA1/2 and other genes (CHEK2, HOXB13, PALB2), including Lynch syndrome genes (MLH1, MSH2, MSH6, and PMS2) in men with metastatic prostate cancer.
These findings indicate that BRCA1 interacts with the components of the JAK-STAT signaling cascade and modulates its activation, which may provide a new critical survival signal for the growth of breast, ovarian and prostate cancers in the presence of normal BRCA1.
The data suggest that the region distal to BRCA1 may contain 1 or more prostate-specific tumor suppressor genes and that BRCA1 itself plays only a minor role in prostate cancer development.
Examination of other breast and prostate cancer cell lines revealed that sensitivity to the anti-proliferative effects of 1alpha, 25(OH)2D3 was strongly associated with an ability to modulate BRCA1 protein.
To date, National Comprehensive Cancer Network (NCCN) guidelines have highly selective criteria for BRCA1/2 testing for men with prostate cancer based on personal history and/or specific family cancer history.
Our data suggest that the BRCA1 and/or other genes within the interval between BRCA1 and D17S856 on 17q21 may be important in the pathogenesis of prostate cancer.
In order to substantiate the data for BRCA1 gene loss in PCa and reveal its phenotypical background, BRCA1 gene status was assessed in a large cohort of PCa patients and compared to different molecular factors.
Our results suggest that a potential tumor suppressor gene(s) may reside in the < 2 Mb region centromeric (inclusive) to the BRCA1 gene and that this tumor suppressor gene(s) may be involved in the formation of prostate cancer.
BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood.
Present study demonstrated that BRCA1 and EZH2 are coregulated in patients' tumors and PCa cell lines, and cooperate in regulation of CSC phenotype and properties.
These data suggest that microsatellite instability and loss of unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate; however, BRCA1 and BRCA2 may not be largely involved in the development of prostate cancer in the Japanese population.