1431 EPIGENETIC REGULATION OF MYOPODIN GENE IN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research VIII1 Apr 20101431 EPIGENETIC REGULATION OF MYOPODIN GENE IN PROSTATE CANCER Temuujin Dansranjavin, Florian Wagenlehner, Alexander Bogumil, Bora Altinkilic, Wolfgang Weidner, Klaus Steger, and Agnieszka Paradowska Temuujin DansranjavinTemuujin Dansranjavin More articles by this author , Florian WagenlehnerFlorian Wagenlehner More articles by this author , Alexander BogumilAlexander Bogumil More articles by this author , Bora AltinkilicBora Altinkilic More articles by this author , Wolfgang WeidnerWolfgang Weidner More articles by this author , Klaus StegerKlaus Steger More articles by this author , and Agnieszka ParadowskaAgnieszka Paradowska More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1124AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Myopodin is an actin binding protein frequently down regulated in prostate cancers (PCa) and PCa derived cell lines. Overexpression of myopodin inhibits PCa growth and metastasis in-vitro and in-vivo. However, less is known about the molecular mechanism underlying the regulation of myopodin gene expression. In this study, we analyzed the involvement of epigenetic mechanisms in PCa-associated regulation of myopodin. METHODS To evaluate the role of epigenetic DNA/histone modifications in the silencing of myopodin gene in PCa, we analyzed the effect of 5-aza-2-deoxycytidine (5-aza-dC) and trichostatin A (TSA) on myopodin mRNA expression in PCa cell lines 22RV1, LNCAP and DU145. Combined bisulfite restriction analysis (COBRA) and bisulfite sequencing of myopodin gene promoter were performed on frozen tissue samples from 37 PCa patients (18 T2, 14 T3, 5 T4) containing 20 of benign prostatic hyperplasia (BPH), 17 of prostate adenocarcinoma. The myopodin mRNA expression levels were examined in relation to methylation status of myopodin gene promoter and clinicopathological parameters of PCa patients. RESULTS All examined PCa cell lines revealed partial methylation of myopodin gene promoter associated with weak (LnCAP) and lack (DU145, 22RV1) of mRNA expression. Myopodin mRNA expression was inducible by TSA. The effect of TSA was enhanced by a combined treatment with 5-aza-dC in DU145 and LNCAP. 59% (10/17) of PCa and 65% (13/20) of BPH revealed a partial methylation of myopodin gene promoter. All matched samples of stromal tissue with PCa (12) and HGPIN with BPH (5) revealed concordant methylation pattern. Among T3-PCa a gradual loss of methylation with increasing dedifferentiation was observed (80% in G2 vs. 44% in G3). CONCLUSIONS Silenced myopodin gene was inducible with TSA and with combined treatment with TSA and 5-aza-dC. These results indicate that epigenetic histone and DNA modifications are involved in PCa associated myopodin inactivation. Partial methylation of myopodin may indicate at histological dedifferentiation in advanced PCa. Giessen, Germany© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e551-e552 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Temuujin Dansranjavin More articles by this author Florian Wagenlehner More articles by this author Alexander Bogumil More articles by this author Bora Altinkilic More articles by this author Wolfgang Weidner More articles by this author Klaus Steger More articles by this author Agnieszka Paradowska More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...