| First Author | Yang YA | Year | 2006 |
| Journal | Cancer Cell | Volume | 9 |
| Issue | 6 | Pages | 445-57 |
| PubMed ID | 16766264 | Mgi Jnum | J:110133 |
| Mgi Id | MGI:3639400 | Doi | 10.1016/j.ccr.2006.04.025 |
| Citation | Yang YA, et al. (2006) Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2. Cancer Cell 9(6):445-57 |
| abstractText | 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. |
