Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis

Rami I. Aqeilan, John P. Hagan, Alain De Bruin, Maysoon Rawahneh, Zaidoun Salah, Eugenio Gaudio, Hasan Siddiqui, Stefano Volinia, Hansjuerg Alder, Jane B. Lian, Gary S. Stein, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

The WW domain-containing oxidoreductase (WWOX) gene encodes a 46-kDa tumor suppressor. The Wwox protein contains two N-terminal WW domains that interact with several transcriptional activators containing proline-tyrosine motifs and a central short-chain dehydrogenase/reductase domain that has been suggested to play a role in steroid metabolism. Recently, we have shown that targeted deletion of the Wwox gene in mice leads to postnatal lethality and defects in bone growth. Here, we report that MAvox-deficient mice display impaired steroidogenesis. Mutant homozygous mice are born with gonadal abnormalities, including failure of Leydig cell development in testis and reduced theca cell proliferation in ovary. Furthermore, Wwox -/-mice displayed impaired gene expression of key steroidogenesis enzymes. Affymetrix microarray gene analysis revealed differentially expressed related genes in steroidogenesis in knockout mice testis and ovary as compared with control mice. These results demonstrate the essential requirement for the Wwox tumor suppressor in proper steroidogenesis.

Original languageAmerican English
Pages (from-to)1530-1535
Number of pages6
JournalEndocrinology
Volume150
Issue number3
DOIs
StatePublished - Mar 2009

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