Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2
| Autor: | Gen-mu Zhang, Yu-an Yang, Lionel Feigenbaum, Ying E. Zhang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Transcription Genetic p38 mitogen-activated protein kinases Transgene Down-Regulation Apoptosis Mice Transgenic Biology p38 Mitogen-Activated Protein Kinases Article Mice Liver Neoplasms Experimental Mediator Downregulation and upregulation Transforming Growth Factor beta In vivo Animals Smad3 Protein Promoter Regions Genetic Cells Cultured Cell Biology Transforming growth factor beta Protein Transport Proto-Oncogene Proteins c-bcl-2 Oncology Hepatocytes Cancer research biology.protein Disease Susceptibility Signal transduction Signal Transduction |
| Zdroj: | Cancer Cell. 9:445-457 |
| ISSN: | 1535-6108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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