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Transforming Growth Factor-Beta-1 Is a New Form of Tumor Suppressor With True Haploid Insufficiency

  1. Author:
    Tang, B. W.
    Bottinger, E. P.
    Jakowlew, S. B.
    Bagnall, K. M.
    Mariano, J.
    Anver, M. R.
    Letterio, J. J.
    Wakefield, L. M.
    1. Year: 1998
  2. Journal: Nature Medicine
    1. 4
    2. 7
    3. Pages: 802-807
  4. Type of Article: Article
  1. Abstract:

    Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-beta s themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta 1 gene express only 10-30% of wild-type TGF-beta 1 protein levels. Although grossly normal, these mice have a subtly altered proliferative phenotype, with increased cell turnover in the liver and lung. Treatment of these mice with chemical carcinogens resulted in enhanced tumorigenesis when compared with wild-type littermates. However, tumors in the heterozygous mice did not lose the remaining wild-type TGF-beta 1 allele, indicating that the TCF-beta 1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis. [References: 45]

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