Expression of BRCA1 and FAC1 in primary sporadic breast cancers.

Abstract

We have previously described a +ACA BRCA1 promoter polymorphism that creates a FAC1 transcriptional repressor binding site (AACAACAC), which may confer FAC1‐mediated transcriptional repression (depending on the BRCA1 promoter genotype). To explore the relationship between BRCA1 and FAC1 expression in primary breast cancers, we performed immunostaining on 69 luminal A and B subtype sporadic breast cancers (ER+, PR+, HER2+/−). Most tumors are positive for BRCA1 expression (40/69, 58%), while a subset express reduced BRCA1 levels (29/69, 42%). The majority of these tumors (64/69, 93%) are positive for FAC1 expression: 27/64 (42%) express cytoplasmic FAC1 (cFAC1), 23/64 (36%) express both cFAC1 and nuclear FAC1 (nFAC1) and 14/64 (22%) express nFAC1 only. Among tumors with reduced BRCA1 expression, 55% (16/29) are positive for nFAC1 expression (which represents 43% (16/37) of nFAC1 expressing tumors that have reduced BRCA1 protein expression). This data suggests that most primary breast tumors are positive for FAC1 expression, and that 58% of FAC1 expressing tumors have some degree of nuclear FAC1 expression. It is intriguing to speculate that nFAC1 may modify gene expression in breast tumors, resulting in repression of normal BRCA1 expression, and contributing to breast carcinogenesis.Support: NIH CA78343, Komen Foundation BCTR0100575, Friends For an Earlier Breast Cancer Test.