Phytoestrogens regulate the expression of genes involved in different biological processes in BRCA2 knocked down...

Breast cancer is a public health problem in the Western countries. Several studies have shown that BRCA2, like BRCA1 oncosuppressors, are strongly involved in hereditary and sporadic mammary carcinogenesis. It has also been suggested that soy has a protective effect against breast cancer in Asia and, more particularly, phytoestrogens such as daidzein and genistein. Thus, phytoestrogens may have an impact on the expression of BRCA2 gene, and there is a possible link between BRCA2 and genes acting around the BRCA2. To focus on these processes, we set up the BRCA2 specific knockdown by RNA interference in two breast tumor cell lines (MCF-7 and MDA-MB-231) and also in a non-tumorigenic breast cell line (MCF-10a). After inhibition of BRCA2 expression, cells were maintained in different conditions and treated with either daidzein or genistein or left untreated. Microarray analysis of mRNAs isolated from the BRCA2 knocked down MCF-7, MDA-MB-231, and MCF-10a cell lines after being treated with phytoestrogens showed 35 differentially expressed genes between positive-ERbeta cells and negative-ERbeta cells. After genistein or daidzein treatments, BRCA1 was found to be up-regulated when knocked down with BRCA2-siRNA MCF-7 and BRCA2 was found to be up-regulated when knocked down with BRCA2-siRNA MDA-MB 231 cells. In MCF-10a, we observed a significant decrease in BAX and BCL2 expressions with a greater effect of daidzein. We also found an increase in BRIP expression between genistein and daidzein treatment knocked down with BRCA2-siRNA MCF-7 and MDA-MB-231 cell lines.