Characterization of WWOX inactivation in murine mammary gland development1. Issue 7 (21st March 2013)

• Record Type: Journal Article
• Authors: Abdeen, Suhaib K.; Salah, Zaidoun; Khawaled, Saleh; Aqeilan, Rami I.
• Is Part Of: Journal of cellular physiology. Volume 228:Issue 7(2013:Jul.)
• Page Start: 1391
• Page End: 1396
• Publication Date: 2013-03-21
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24310
• Languages: English
• ISSNs: 0021-9541

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The WW domain‐containing oxidoreductase (WWOX) is commonly inactivated in multiple human cancers, including breast cancer. <italic>Wwox</italic> null mice die prematurely precluding adult tumor analysis. Nevertheless, aging <italic>Wwox</italic>‐heterozygous mice at C3H genetic background develop higher incidence of mammary tumors. We recently generated a <italic>Wwox</italic> conditional knockout mouse in which loxp sites flank exon 1 in the <italic>Wwox</italic> allele and showed that total ablation of WWOX in these mice resembles that of conventional targeting of <italic>Wwox</italic>. Here, we report the characterization of WWOX ablation in mouse mammary gland using <italic>MMTV‐Cre</italic> transgenic line. We demonstrated that WWOX ablation leads to impaired mammary ductal growth. Moreover, targeted deletion of WWOX is associated with increased levels of fibronectin, a component of the extracellular matrix. In addition, we showed that shRNA knockdown of WWOX in MCF10A breast epithelial cells dramatically increased fibronectin and is associated with enhanced cell survival and impaired growth in three‐dimensional culture Matrigel assay. Taken together our results are consistent with a critical role for WWOX in normal breast development and tumorigenesis. J. Cell. Physiol. 228: 1391–1396, 2013. © 2012 Wiley Periodicals, Inc.</p> </abstract>