Transforming Growth factor-beta1 Is a New Form of Tumor Suppressor With True Haploid Insufficiency

Nat Med. 1998 Jul;4(7):802-7. doi: 10.1038/nm0798-802.

Abstract

Components of the transforming growth factor-beta (TGF-beta) signal pathway function as classic tumor suppressors, but the role of the TGF-betas themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-beta1 gene express only 10-30% of wild-type TGF-beta1 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-beta1 allele, indicating that the TGF-beta1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenicity Tests
  • Cell Cycle Proteins / genetics
  • Cell Division
  • Gene Targeting
  • Genes, Tumor Suppressor*
  • Liver / cytology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism

Substances

  • Cell Cycle Proteins
  • Transforming Growth Factor beta