249 ZEB1 IS ESTROGEN RESPONSIVE IN VITRO IN HUMAN FORESKIN CELLS AND IS OVEREXPRESSED IN PENILE SKIN IN PATIENTS WITH SEVERE HYPOSPADIAS

Abstract

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2011249 ZEB1 IS ESTROGEN RESPONSIVE IN VITRO IN HUMAN FORESKIN CELLS AND IS OVEREXPRESSED IN PENILE SKIN IN PATIENTS WITH SEVERE HYPOSPADIAS Liang Qiao, Gregory Tasian, Zhang Haiyang, Gerald Cunha, and Laurence Baskin Liang QiaoLiang Qiao San Francisco, CA More articles by this author , Gregory TasianGregory Tasian San Francisco, CA More articles by this author , Zhang HaiyangZhang Haiyang 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.2011.02.340AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES ZEB1, which acts as a transcriptional repressor and down-regulates cellular adhesion molecules, is one of many genes upregulated in patients with isolated hypospadias. This study determined the effect of estrogen on ZEB1 expression in vitro and tested the hypothesis that ZEB1 expression in penile skin is overexpressed in subjects with hypospadias. METHODS Hs68 cells, a fibroblast cell line derived from human foreskin, were exposed to 0, 1, 10, and 100nm of estrogen, after which the expression level of ZEB1 was assessed using reverse transcription real-time PCR, Western blot, and immunocytochemistry. Secondly, preputial skin was prospectively collected from case and control human subjects at the time of hypospadias repair (n = 37) and circumcision (n = 11), respectively. Hypospadias was classified as severe (n = 13) or mild (n = 24) based on position of the urethral meatus. ZEB1 expression was quantified using reverse transcription real-time PCR, Western blot and immunohistochemistry. RESULTS Estrogen increased ZEB1 expression at the mRNA and protein level in Hs68 cells in a concentration-dependent fashion (p < 0.01). Subjects with severe hypospadias had significantly higher ZEB1 mRNA levels and protein expression compared to control subjects and subjects with mild hypospadias (all p < 0.01). Subjects with severe hypospadias have increased expression of ZEB1 in the basal layers of the preputial epidermis. CONCLUSIONS Estrogen increases ZEB1 expression in a human foreskin fibroblast cell line in vitro. Furthermore, zeb1 is significantly over-expressed in the penile skin of subjects with severe hypospadias. We propose that ZEB1 overexpression may contribute to the development of hypospadias and may mediate the effect of estrogen on developing external male genitalia. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e100-e101 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Liang Qiao San Francisco, CA More articles by this author Gregory Tasian San Francisco, CA More articles by this author Zhang Haiyang 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 ...