GA-binding protein alpha/beta is a critical regulator of the BRCA1 promoter

Decreased expression of BRCA1 may play a role in the etiology of sporadic b reast cancer. Deletion and point mutant analysis of proximal promoter eleme nts 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 effe ct in T47D cells, The main transcription factor interacting with this site was identified as GABP alpha/beta, and a discrete DNA binding complex was o nly observed in nuclear extracts from MCF-7 cells, Cotransfection experimen ts with GABP alpha and beta 1 expression vectors produced transactivation o f this element in both lines, These results suggest that GABP alpha/beta is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.