Regulation of angiotensin II type 1 receptor expression in ovarian cancer: a potential role for BRCA1

BACKGROUND Both BRCA1 and angiotensin II type 1 receptor (AGTR1) play a critical role in ovarian cancer progression. However, the crosstalk between BRCA1 and AGTR1 signaling pathways remains largely unknown. METHODS BRCA1 promoter methylation was analyzed by bisulfite sequence using primers focused on the core promoter region. Expression levels of BRCA1 and AGTR1 were assessed by immunohistochemistry and real-time PCR. Regression analysis was used to examine the possible relationship between BRCA1 and AGTR1 protein levels. Knockdown or overexpression of BRCA1 was achieved by using a lentiviral vector in 293 T cells and SKOV3 ovarian carcinoma cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells. RESULTS BRCA1 dysfunction (BRCA1 mutation or hypermethylated BRCA1 promoter) ovarian cancer showed decreased AGTR1 levels compared to normal tissue. In contrast, AGTR1 expression was increased in non-BRCA1-mutated ovarian cancer. Notably, BRCA1 activation was an effective way to induce AGTR1 expression in primary ovarian cancer cells and a positive correlation exists between BRCA1 and AGTR1 expression in human ovarian cancer specimens. CONCLUSIONS These results indicate that BRCA1 may be a potential trigger involved in the transcriptional regulation of AGTR1 in the development of ovarian cancer.