Abstract

The breast cancer susceptibility gene BRCA1 on chromosome 17q21 encodes an 1863 amino acid protein that is important for normal embryonic development. Germline mutations of this gene are linked to a significantly increased lifetime risk for breast and/or ovarian cancer, and recent studies suggest that the same may be true for prostate cancer. Several activities that may contribute to the tumor suppressor function of BRCA1 have been identified via in vitro and experimental animal studies. These include (i) regulation of cell proliferation; (ii) participation in DNA repair/recombination processes related to the maintenance of genomic integrity; (iii) induction of apoptosis in damaged cells; and (iv) regulation of transcription. A second breast cancer susceptibility gene (BRCA2) operates in some of the same molecular pathways as BRCA1, and mutations of this gene predispose to breast and ovarian cancer and probably to other tumor types, including prostate cancer. Finally, recent studies from our laboratory suggest that BRCA1 modulates proliferation, chemosensitivity, repair of DNA strand breaks, apoptosis induction, and expression of certain key cellular regulatory proteins (including BRCA2 and p300) in human prostate cancer cells. These activities are consistent with a putative prostate tumor suppressor function of BRCA1.