Hint1 is a haplo-insufficient tumor suppressor in mice
- 26 September 2005
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 25 (5) , 713-721
- https://doi.org/10.1038/sj.onc.1209111
Abstract
The HINT1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. However, its precise function in mammalian cells is not known. As a result of its structural similarity to the tumor-suppressor protein FHIT, we used homozygous-deleted Hint1 mice to study its role in tumorigenesis. We discovered that after 2 to 3 years of age the spontaneous tumor incidence in Hint1 −/− mice was significantly greater than that in wild-type Hint1 +/+ mice (PPHint1 −/− and +/− mice versus +/+ mice. The Hint1 −/− and +/− mice had similar tumor incidence and similar tumor histologies. Therefore, deletion of Hint1 in mice enhances both spontaneous tumor development and susceptibility to tumor induction by DMBA. In addition, since the Hint1 +/− tumors retained expression of the unmutated wild-type allele, Hint1 is haplo-insufficient with respect to tumor suppression in this model system.Keywords
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