Abstract
<div>Abstract<p>The expression of the <i>WWOX</i> tumor suppressor gene is lost or reduced in a large fraction of various cancers, including prostate cancer. We previously reported that Wwox overexpression induced apoptosis and suppressed prostate cancer growth <i>in vitro</i> and <i>in vivo</i>. In this study, pathways through which Wwox contributes to control of prostate cancer cell growth have been investigated. We found that Wwox interacts with Ap2γ and prevents it from entering the nucleus to bind the <i>ERBB2</i> promoter region to activate transcription of <i>ERBB2</i>, a mediator of androgen receptor activity and prostate cancer cell growth at limiting androgen concentration. Ectopic expression of Wwox reduced ErbB2 protein expression <i>in vitro</i> and expression of Wwox protein inversely correlated with expression of ErbB2 protein in prostate cancer tissues. Furthermore, Wwox suppressed Ap2γ/ErbB2–induced prostate cancer cell growth and suppressed prostate-specific antigen secretion through interaction with Ap2γ and down-modulation of ErbB2, an effect that required functional androgen receptor. (Mol Cancer Res 2007;5(9):957–65)</p></div>
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