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Publication : Targeted deletion of Wwox reveals a tumor suppressor function.

First Author  Aqeilan RI Year  2007
Journal  Proc Natl Acad Sci U S A Volume  104
Issue  10 Pages  3949-54
PubMed ID  17360458 Mgi Jnum  J:120064
Mgi Id  MGI:3703820 Doi  10.1073/pnas.0609783104
Citation  Aqeilan RI, et al. (2007) Targeted deletion of Wwox reveals a tumor suppressor function. Proc Natl Acad Sci U S A 104(10):3949-54
abstractText  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.
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