Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced effect in T47D cells. The main transcription factor interacting with this site was identified as GABPalpha/beta, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPalpha and beta1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPalpha/beta is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.