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Knockout mice reveal a tumor suppressor function for Testin.

Alessandra Drusco·Nicola Zanesi·Claudia Roldo·Francesco Trapasso·John L Farber·Louise Y Fong·Carlo M Croce
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Abstract

The Testin (TES) gene was previously identified as a putative human tumor suppressor gene at 7q31.2, a region that is frequently deleted in hematopoietic malignancies, as well as in epithelial tumors. To determine whether TES acts as a tumor suppressor in vivo, we generated a Tes knockout mouse and then used it in an established model of carcinogen-induced gastric cancer. In mice a zinc-deficient (ZD) diet enhances cellular proliferation in the forestomach and susceptibility to N-nitrosomethylbenzylamine (NMBA)-induced carcinogenesis. Five-week-old Tes wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice were divided into four groups: mice fed a zinc-sufficient diet (ZS); mice fed a ZD diet; ZS fed plus NMBA-treated mice (ZS+NMBA), and ZD fed plus NMBA-treated mice (ZD+NMBA). After 4 weeks, the ZS+NMBA and ZD+NMBA groups were treated with three intragastric doses of NMBA. Animals were killed 8 weeks after NMBA administration: 25% of +/+ mice developed benign lesions; 88% of +/- showed multiple papillomas, atypical glandular metaplasia, and squamous cell carcinomasl; and 81% of -/- mice displayed very large papillomas, squamous cell carcinomas, and adenocarcinomas. A statistically significant difference in tumor incidence was found between +/- versus +/+ and -/- versus +/+ (P < 0.0001). These data suggest that Tes functions as a tumor suppressor gene in vivo.

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AdenocarcinomaAnimalsBase SequenceCarcinogensCarcinoma, Squamous CellCytoskeletal ProteinsDNADNA-Binding ProteinsDimethylnitrosamineFemaleGenes, Tumor SuppressorMaleMetaplasiaMiceMice, Inbred C57BLMice, KnockoutPapillomaRNA-Binding ProteinsStomach NeoplasmsTumor Suppressor ProteinsZincJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov't, P.H.S.

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Alessandra Drusco, Nicola Zanesi, Claudia Roldo, Francesco Trapasso, John L Farber, Louise Y Fong, Carlo M Croce. 2005-07-20. Knockout mice reveal a tumor suppressor function for Testin.. https://doi.org/10.1073/pnas.0504934102

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