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Targeted deletion of Wwox reveals a tumor suppressor function.

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.

Pubmed ID: 17360458


  • Aqeilan RI
  • Trapasso F
  • Hussain S
  • Costinean S
  • Marshall D
  • Pekarsky Y
  • Hagan JP
  • Zanesi N
  • Kaou M
  • Stein GS
  • Lian JB
  • Croce CM


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 6, 2007

Associated Grants

  • Agency: NIAMS NIH HHS, Id: P01 AR 048818
  • Agency: NIAMS NIH HHS, Id: P01 AR048818
  • Agency: NCI NIH HHS, Id: P01 CA 082834

Mesh Terms

  • Animals
  • Carcinoma
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Genome
  • Humans
  • Lung Neoplasms
  • Lymphoma
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Osteosarcoma
  • Oxidoreductases
  • Phenotype