Skip NavigationSkip to Content
Return Return to Search Results

Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2

  1. Author:
    Yang, Y. A.
    Zhang, G. M.
    Feigenbaum, L.
    Zhang, Y. E.

  2. Author Address

    NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Anim Sci Program, Frederick, MD 21702 USA.;Zhang, YE, NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.;yingz@helix.nih.gov
    1. Year: 2006
    2. Date: Jun
  2. Journal: Cancer Cell
    1. 9
    2. 6
    3. Pages: 445-457
  4. Type of Article: Article
  5. ISSN: 1535-6108
  1. 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.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.ccr.2006.04.025
  3. View record in Web of Science®
  4. WOS: 000238514400006

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel