Abstract

BRCA1 was originally isolated as a gene that conferred susceptibility to early-onset familial breast and ovarian cancers. The function and regulation of this gene is presently unknown. Northern blot analyses using probes that recognize different regions of the BRCA1 cDNA revealed the presence of at least two distinct mRNA species. In synchronized normal and immortalized human mammary epithelial cells, BRCA1 mRNA levels were high in exponentially growing populations, decreased upon growth factor withdrawal, and subsequently increased again in late G1 just prior to S-phase entry. BRCA1 mRNA levels were found to be dramatically reduced in senescent normal human mammary epithelial cells and in normal human mammary epithelial cells treated with transforming growth factor beta 1. When considered together, these data indicate that expression of BRCA1 mRNA is highly sensitive to changes in growth conditions in vitro. BRCA1 proteins with apparent molecular weights of M(r) 210,000, 185,000, 160,000, 135,000, and 85,000, respectively, were detected at varying levels in all breast epithelial cells examined. Further molecular characterization of the nature and function of the different BRCA1 mRNAs and proteins should increase our understanding of this gene in the etiology of human breast cancers.