Abstract
At the moment, breast cancer is a public health problem in the Western countries. Several studies have shown that BRCA2, like BRCA1 oncosuppressors, are heavily involved in the processes of hereditary and sporadic mammary carcinogenesis. It has also been suggested that soy has a protective effect against breast cancer in Asia, and more particularly that phytoestrogen, such as daidzein and genistein, has this effect. Given this, it is interesting to see if phytoestrogens have an impact on the expression of BRCA2 gene. In addition, it is important to show the possible links between BRCA2 gene and genes acting around BRCA2. To focus on all these processes, we set up the BRCA2 specific knock down by RNA interference in two breast tumor cell lines (MCF-7 and MDA-MB-231) and also in a non-tumorogenic breast cell line (MCF-10a). After inhibition of BRCA2 expression, cells were maintained in different conditions and treated with either daidzein, genistein, or left untreated. Microarray analysis of mRNAs isolated from the BRCA2 knocked down MCF-7, MDA-MB-231, and MCF-10a cell lines treated with phytoestrogens, showed 35 differentially expressed genes between ER\#946;-positive and ER\#946;-negative cells. After genistein or daidzein treatments, BRCA1 was found to be up-regulated in MCF7 knocked down with BRCA2-siRNA. In MDA-MB 231 cells knocked down with BRCA2-siRNA, BRCA2 were found to be up-regulated after isoflavone treatments. In MCF-10a cell line, we observed a significant decrease in BAX and BCL2 expressions with an even greater effect when treated with daidzein. We also found an increase in BRIP expression between genistein and daidzein treatments in MCF-7 and MDA-MB-231 cell lines knocked down with BRCA2-siRNA.
Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5303.
100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO