| Literature DB >> 17360458 |
Rami I Aqeilan1, Francesco Trapasso, Sadiq Hussain, Stefan Costinean, Dean Marshall, Yuri Pekarsky, John P Hagan, Nicola Zanesi, Mohamed Kaou, Gary S Stein, Jane B Lian, Carlo M Croce.
Abstract
The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox(-/-) and lung papillary carcinoma in adult Wwox(+/-) mice occurred spontaneously. In addition, Wwox(+/-) mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.Entities:
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Year: 2007 PMID： 17360458 PMCID： PMC1820689 DOI： 10.1073/pnas.0609783104
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205