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

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2008 Nov 1

PMID 18974271

Citations 46

Authors

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

Affiliations

Soon will be listed here.

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 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.

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