Skip NavigationSkip to Content
Return Return to Search Results

Transforming growth factor-beta can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model

  1. Author:
    Tang, B.
    Yoo, N.
    Vu, M.
    Mamura, M.
    Nam, J. S.
    Ooshima, A.
    Du, Z.
    Desprez, P. Y.
    Anver, M. R.
    Michalowska, A. M.
    Shih, J.
    Parks, W. T.
    Wakefield, L. M.

  2. Author Address

    NCI, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA 94115 USA. NCI, Pathol Histotechnol Lab, Frederick, MD 21701 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA.;Wakefield, LM, Gachon Univ Med Sci, Canc & Diabet Inst, Inchon 406840, South Korea.;lw34g@nih.gov
    1. Year: 2007
    2. Date: Sep
  2. Journal: Cancer Research
    1. 67
    2. 18
    3. Pages: 8643-8652
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    The transforming growth factor-beta (TGF-beta) pathway has tumor-suppressor activity in many epithelial tissues. Because TGF-beta is a potent inhibitor of epithelial cell proliferation, it has been widely assumed that this property underlies the tumor-suppressor effect. Here, we have used a xenograft model of breast cancer to show that endogenous TGF-beta has the potential to suppress tumorigenesis through a novel mechanism, involving effects at two distinct levels in the hierarchy of cellular progeny that make up the epithelial component of the tumor. First, TGF-beta reduces the size of the putative cancer stem or early progenitor cell population, and second it promotes differentiation of a more committed, but highly proliferative, progenitor cell population to an intrinsically less proliferative state. We further show that reduced expression of the type II TGF-beta receptor correlates with loss of luminal differentiation in a clinical breast cancer cohort, suggesting that this mechanism may be clinically relevant. At a molecular level, the induction of differentiation by TGF-beta involves down-regulation of Id1, and forced overexpression of Id1 can promote tumorigenesis despite persistence of the antiproliferative effect of TGF-beta. These data suggest new roles for the TGF-beta pathway in regulating tumor cell dynamics that are independent of direct effects on proliferation.

    See More

  1. Keywords:

External Sources

  1. View record in Web of Science®
  2. WOS: 000249679500029

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