Induction of apoptosis by the tumor suppressor protein BRCA1.

The breast and ovarian cancer susceptibility gene BRCA1, is a nuclear phosphoprotein which functions as a tumor suppressor. To investigate the role of BRCA1 in apoptosis, we have developed mouse fibroblast cell lines and human breast cancer cell lines expressing BRCA1. The expression of BRCA1 protein in the BRCA1 transfectants were analysed by immunofluorescence and immunohistochemistry. The BRCA1 transfectants showed a flattened morphology compared to the parental cells. We show that serum deprivation or calcium ionophore treatment of BRCA1 transfectants resulted in programmed cell death. These results indicate that BRCA1 genes may play a critical role in the regulation of apoptosis. Thus, since a wide variety of human malignancies like breast and ovarian cancers have a decreased ability to undergo apoptosis, this could be due to lack/decreased levels of functional BRCA1 proteins. Treatments that are aimed at increasing the apoptotic threshold by BRCA1 gene therapy may have the potential to prevent the progression of these malignancies.