Abstract
BackgroundBoth 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.MethodsBRCA1 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.ResultsBRCA1 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.ConclusionsThese results indicate that BRCA1 may be a potential trigger involved in the transcriptional regulation of AGTR1 in the development of ovarian cancer.
Highlights
Both BRCA1 and angiotensin II type 1 receptor (AGTR1) play a critical role in ovarian cancer progression
All patients were screened for BRCA1 mutations by multiplex polymerase chain reaction (PCR) with complete sequence analysis using methods reported by Bi and Simard [15,16], Their characteristics are given in Additional file 1: Table S1
BRCA1 can regulate Angiotensin II type 1 receptor (AGTR1) expression in primary ovarian cancer cells To confirm the role of BRCA1 in the regulation of AGTR1, the effects of overexpression or knockdown of BRCA1 were observed in 293 T cells, human ovarian carcinoma cell line SKOV3, primary ovarian cancer cells with identified BRCA1 mutations or non-mutation
Summary
Both BRCA1 and angiotensin II type 1 receptor (AGTR1) play a critical role in ovarian cancer progression. The crosstalk between BRCA1 and AGTR1 signaling pathways remains largely unknown. The exact cause of ovarian cancer remains largely unknown, BRCA mutations are the main known hereditary factor [2], and the risk of ovarian cancer conferred by BRCA mutations can be regulated by both genetic and environmental components [3]. AGTR1 has drawn considerable interest, in the field of cardiovascular risk and in several types of gynecological malignancies, such as endometrial cancer [5,6], cervical carcinoma [7], and especially ovarian cancer [8,9,10].
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