References
Query Results -- Details
MGI Accession ID: MGI:3639400
J Number: J:110133
Other Accession IDs:
Title: Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2.
Authors: Yang YA; Zhang GM; Feigenbaum L; Zhang YE
Journal: Cancer Cell
Volume: 9
Issue: 6
Date: 2006 Jun
Year: 2006
Pages: 445-57
Review Status: Peer Reviewed
Abstract:
In the liver, derangement of TGF-beta signaling is associated with an increased incidence of hepatocellular carcinoma (HCC), but the mechanism is not clear. We report here that forced expression of a major TGF-beta signaling transducer, Smad3, reduces susceptibility to HCC in a chemically induced murine model. This protection is conferred by Smad3's ability to promote apoptosis by repressing Bcl-2 transcription in vivo through a GC-rich element in the Bcl-2 promoter. We also show that the proapoptotic activity of Smad3 requires both input from TGF-beta signaling and activation of p38 MAPK, which occurs selectively in the liver tumor cells. Thus, Smad3 enables the tumor suppression function of TGF-beta by serving as a physiological mediator of TGF-beta-induced apoptosis.
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