1521 ANDROGEN RECEPTOR IS OVEREXPRESSED IN BOYS WITH SEVERE HYPOSPADIAS AND ZEB1 REGULATES ANDROGEN RECEPTOR EXPRESSION IN HUMAN FORESKIN CELLS

Abstract

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Lower Urinary Tract & Genitalia I1 Apr 20121521 ANDROGEN RECEPTOR IS OVEREXPRESSED IN BOYS WITH SEVERE HYPOSPADIAS AND ZEB1 REGULATES ANDROGEN RECEPTOR EXPRESSION IN HUMAN FORESKIN CELLS Liang Qiao, Gregory Tasian, Haiyang Zhang, Mei Cao, Max Ferretti, Gerald Cunha, and Laurence Baskin Liang QiaoLiang Qiao Shandong, China, People's Republic of More articles by this author , Gregory TasianGregory Tasian Philadelphia, PA More articles by this author , Haiyang ZhangHaiyang Zhang San Francisco, CA More articles by this author , Mei CaoMei Cao San Francisco, CA More articles by this author , Max FerrettiMax Ferretti San Francisco, CA More articles by this author , Gerald CunhaGerald Cunha San Francisco, CA More articles by this author , and Laurence BaskinLaurence Baskin San Francisco, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1289AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies have shown that ZEB1 is overexpressed in patients with severe hypospadias. We sought to examine the interaction between ZEB1 and the androgen receptor (AR) in vitro and determine if AR is overexpressed in boys with hypospadias. METHODS Hs68 cells, a fibroblast cell line derived from neonatal human foreskin, were exposed to 0, 10, and 100nM of estrogen, after which the expression level of AR mRNA and protein was assessed using real-time PCR and Western Blot. The cellular localization of ZEB1 and AR was assessed using immunocytochemistry. To determine if ZEB1 interacted with the AR gene, chromatin immunoprecipitation (ChIP) was performed using ZEB1 antibody and polymerase chain reaction (PCR) for AR. Secondly, AR expression was quantified using real-time PCR and Western blot in normal subjects (n = 32), and subjects with mild (n = 16) and severe hypospadias (n = 16). RESULTS ZEB1 and AR co-localized to the nucleus. Estrogen upregulated AR mRNA expression in Hs68 cells (Figure 1). ChIP demonstrated that ZEB1 binds to an E-box sequence in the AR gene promoter. AR expression is higher in subjects with severe hypospadias than those with mild hypospadias and control subjects (p < 0.05) (Figure 2). CONCLUSIONS Boys with severe hypospadias have elevated AR expression in preputial skin, which correlates directly with ZEB1 expression. ZEB1 physically interacts with AR in human foreskin cells. Estrogenic compounds may increase the risk of hypospadias by facilitating the interaction between ZEB1 and AR. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e615-e616 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Liang Qiao Shandong, China, People's Republic of More articles by this author Gregory Tasian Philadelphia, PA More articles by this author Haiyang Zhang San Francisco, CA More articles by this author Mei Cao San Francisco, CA More articles by this author Max Ferretti San Francisco, CA More articles by this author Gerald Cunha San Francisco, CA More articles by this author Laurence Baskin San Francisco, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...