Transforming growth factor-1 is a new form of tumor suppressor with true haploid insufficiency

Components of the transforming growth factor- (TGF-) signal pathway function as classic tumor suppressors, but the role of the TGF-s themselves is less clear. Here we show that mice heterozygous for deletion of the TGF-1 gene express only 10−30% of wild-type TGF-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-1 allele, indicating that the TGF-1 ligand is a new form of tumor suppressor that shows true haploid insufficiency in its ability to protect against tumorigenesis.

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