A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element

Transcriptional regulation of the BRCA1 proximal promoter has been suggeste d to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter r eveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 an d T-47D cells. This site is shown to be important for the constitutive expr ession of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP ind uction. It appears that CREB acts as a constitutive positive element for BR CA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.