Document Detail


Targeted deletion of Wwox reveals a tumor suppressor function.
MedLine Citation:
PMID:  17360458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rami I Aqeilan; 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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-27
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-15     Completed Date:  2007-04-24     Revised Date:  2014-10-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3949-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma / genetics,  metabolism
Gene Deletion*
Gene Expression Regulation, Neoplastic*
Genes, Tumor Suppressor*
Genome
Humans
Lung Neoplasms / genetics,  metabolism
Lymphoma / genetics,  metabolism
Mice
Mice, Knockout
Mice, Transgenic
Osteosarcoma / metabolism
Oxidoreductases / genetics*
Phenotype
Grant Support
ID/Acronym/Agency:
P01 AR 048818/AR/NIAMS NIH HHS; P01 AR048818/AR/NIAMS NIH HHS; P01 CA 082834/CA/NCI NIH HHS; P01 CA082834/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 1.-/Oxidoreductases; EC 1.-/Wwox protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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