BRCA1 EXPRESSION IS INDUCED BEFORE DNA-SYNTHESIS IN BOTH NORMAL AND TUMOR-DERIVED BREAST CELLS

Insight into the function of the BRCA1 tumor suppressor gene may be ga ined by studying its regulation. In this study, the expression of BRCA 1 was examined as a function of the cell cycle in normal and tumor-der ived breast epithelial cells. Cells arrested in G(0) or early in G(1) contained low levels of BRCA1 mRNA. After release, populations of cell s reached maximal levels of BRCA1 in late G(1) and S phase. Induction of BRCA1 was shown to occur before the onset of DNA synthesis by synch ronizing cells at the G(1)-S boundary. Levels of the BRCA1 protein wer e regulated in a similar manner. No difference was observed between pr imary cultures of normal mammary epithelial cells and immortalized tum or-derived cell lines. These results suggest that BRCA1 may function a t the G(1)-S checkpoint.