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  • Title: TGF-beta1 inhibits BRCA1 expression through a pathway that requires pRb.
    Author: Satterwhite DJ, Matsunami N, White RL.
    Journal: Biochem Biophys Res Commun; 2000 Sep 24; 276(2):686-92. PubMed ID: 11027532.
    Abstract:
    TGF-beta1 inhibits BRCA1 expression, which contradicts the model that TGF-beta1 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-beta1 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-beta1 to inhibit BRCA1 expression. We conclude that TGF-beta1 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-beta1 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-beta1 might alleviate the requirement for BRCA1 function.
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