TGF-beta 1 inhibits BRCA1 expression through a pathway that requires pRb

TGF-beta 1 inhibits BRCA1 expression, which contradicts the model that TGF- beta 1 prevents carcinogenesis by activating tumor suppressor genes. To res olve this apparent contradiction, we examined BRCA1 expression in Mv1Lu cel ls, a well-established model system for studying the TGF-beta 1 tumor suppr essor pathway. We found that inactivation of pRb by the papillomavirus type 16 E7 protein increased BRCA1 expression and abolished the ability of TGF- beta 1 to inhibit BRCA1 expression. We conclude that TGF-beta 1 inhibits BR CA1 expression through a pathway that requires pRb. We propose a model to e xplain the inhibition of BRCA1 as a target in the TGF-beta 1 tumor suppress or signaling pathway. Our results suggest that the tumor suppressor functio ns of BRCA1 are initiated by the inactivation of pRb, and therefore that th e activation of pRb by TGF-beta 1 might alleviate the requirement for BRCA1 function. (C) 2000 Academic Press.