Skip to main content
Article thumbnail
Location of Repository

Targeted Ablation of the WW Domain-Containing Oxidoreductase Tumor Suppressor Leads to Impaired Steroidogenesis

By 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 and Carlo M. Croce


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 Wwox-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

Topics: Article
Publisher: The Endocrine Society
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.