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Transforming growth factor-β1 is a new form of tumor suppressor with true haploid insufficiency

Nature Medicine volume 4, pages 802–807 (1998)Cite this article

Components of the transforming growth factor-β (TGF-β) signal pathway function as classic tumor suppressors, but the role of the TGF-βs themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-β1 gene express only 10–30% of wild-type TGF-β1 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-β1 allele, indicating that the TGF-β1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.

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Author information

Author notes

  1. Erwin P. Böttinger

    Present address: Division of Nephrology U617, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York, 10461, USA

  2. Binwu Tang and Erwin P. Böttinger: B.T. & E.P.B. contributed equally to this work

  3. Lalage M. Wakefield: Correspondence should be addressed to L.M.W.; e-mail: wakefiel@dce41.nci.nih.org

Authors and Affiliations

  1. Laboratory of Cell Regulation and Carcinogenesis (formerly Laboratory of Chemoprevention), National Cancer Institute, 41 LIBRARY DR MSC 5055, Bethesda, Maryland, 20892-5055, USA

    Binwu Tang, Erwin P. Böttinger, Kerri M. Bagnall, John J. Letterio & Lalage M. Wakefield

  2. Cell and Cancer Biology Department, National Cancer Institute, 9610 Medical Center Drive, Rockville, Maryland, 20850, USA

    Sonia B. Jakowlew & Jennifer Mariano

  3. Pathology/Histotechnology Laboratory, Science Applications International Corporation, Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    Miriam R. Anver

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Tang, B., Böttinger, E., Jakowlew, S. et al. Transforming growth factor-β1 is a new form of tumor suppressor with true haploid insufficiency. Nat Med 4, 802–807 (1998). https://doi.org/10.1038/nm0798-802

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