Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 276, Issue 2, Pages 686-692Publisher
ACADEMIC PRESS INC
DOI: 10.1006/bbrc.2000.3510
Keywords
TGF-beta 1; BRCA1; retinoblastoma; papillomavirus; breast cancer; cell cycle; lung
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TGF-beta 1 inhibits BRCA1 expression, which contradicts the model that TGF-beta 1 prevents carcinogenesis by activating tumor suppressor genes. To resolve this apparent contradiction, we examined BRCA1 expression in Mv1Lu cells, a well-established model system for studying the TGF-beta 1 tumor suppressor 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 BRCA1 expression through a pathway that requires pRb. We propose a model to explain the inhibition of BRCA1 as a target in the TGF-beta 1 tumor suppressor signaling pathway. Our results suggest that the tumor suppressor functions of BRCA1 are initiated by the inactivation of pRb, and therefore that the activation of pRb by TGF-beta 1 might alleviate the requirement for BRCA1 function. (C) 2000 Academic Press.
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