| Androgen receptor is overexpressed in boys with severe hypospadias, and ZEB1 regulates androgen receptor expression in human foreskin cells. | |
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MedLine Citation:
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PMID: 22391641 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: ZEB1 is overexpressed in patients with severe hypospadias. We examined the interaction between ZEB1 and the androgen receptor (AR) in vitro and the expression of AR in boys with hypospadias. RESULTS: ZEB1 and AR colocalize to the nucleus. Estrogen upregulated ZEB1 and AR expression. Chromatin immunoprecipitation (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). ZEB1 physically interacts with AR in human foreskin cells. DISCUSSION: AR is overexpressed in patients with severe hypospadias. Environmental estrogenic compounds may increase the risk of hypospadias by facilitating the interaction between ZEB1 and AR. METHODS: Hs68 cells, a fibroblast cell line derived from neonatal human foreskin, were exposed to 0, 10, and 100 nmol/l of estrogen, after which the cellular localization of ZEB1 and AR was assessed using immunocytochemistry. To determine if ZEB1 interacted with the AR gene, ChIP was performed using ZEB1 antibody and polymerase chain reaction (PCR) for AR. Second, AR expression was quantified using real-time PCR and western blot in normal subjects (n = 32), and subjects with mild (n = 16) and severe hypospadia (n = 16). |
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Authors:
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Liang Qiao; Gregory E Tasian; Haiyang Zhang; Mei Cao; Max Ferretti; Gerald R Cunha; Laurence S Baskin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-01-06 |
Journal Detail:
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Title: Pediatric research Volume: 71 ISSN: 1530-0447 ISO Abbreviation: Pediatr. Res. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-06 Completed Date: 2012-07-16 Revised Date: 2013-03-08 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 393-8 Citation Subset: IM |
Affiliation:
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University of California, San Francisco, Department of Urology, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Base Sequence Cell Nucleus / metabolism Chromatin Immunoprecipitation Dose-Response Relationship, Drug Fibroblasts / metabolism Foreskin / metabolism* Gene Expression Regulation* Homeodomain Proteins / biosynthesis*, physiology Humans Hypospadias / metabolism* Male Molecular Sequence Data Promoter Regions, Genetic Receptors, Androgen / biosynthesis*, physiology Transcription Factors / biosynthesis*, physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK058105/DK/NIDDK NIH HHS; R01 DK058105/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Homeodomain Proteins; 0/Receptors, Androgen; 0/Transcription Factors; 0/ZEB1 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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