Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 10, Pages 3949-3954Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0609783104
Keywords
common fragile site; FHIT; knockout; osteosarcoma; lung cancer
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Funding
- NCI NIH HHS [P01 CA 082834, P01 CA082834] Funding Source: Medline
- NIAMS NIH HHS [P01 AR 048818, P01 AR048818] Funding Source: Medline
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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 haploin-suffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.
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