Regulation of the BRCA1 promoter in ovarian surface epithelial cells and ovarian carcinoma cells.

ABSTRACT

As BRCA1 expression is often suppressed in sporadic ovarian carcinoma we characterized the regulation of the 231nt proximal 'L6' fragment of the BRCA1 promoter in two human ovarian surface epithelial cell and two sporadic ovarian carcinoma cell lines. Two individual regulatory elements within L6, the 'RIBS' element and the potential 'CRE' element were each necessary, but alone not sufficient for L6 activation in all four cell lines. The latter element showed some affinity for the CREB transcription factor, but cAMP pathway stimulation failed to promote its activation. This element did, however, interact with, and was activated by, c-Jun and Fra2 which suggests that it can interact with AP1-like transcription factors and that it may act co-operatively with RIBS-binding factors to regulate BRCA1 transcription in ovarian cells.