1131 EPIGENETIC INACTIVATION OF METHYLATION-CONTROLLED J PROTEIN (MCJ) IN BLADDER CANCER

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You have accessJournal of UrologyBladder Cancer: Basic Research (III)1 Apr 20131131 EPIGENETIC INACTIVATION OF METHYLATION-CONTROLLED J PROTEIN (MCJ) IN BLADDER CANCER Noemi Pompas-Veganzones, Virginia Sandonis, Pilar Gonzalez-Peramato, Patricia Moya, Joan Palou, Oscar Rodriguez, Ferran Algaba, Mercedes Rincon, and Marta Sanchez-Carbayo Noemi Pompas-VeganzonesNoemi Pompas-Veganzones Madrid, Spain More articles by this author , Virginia SandonisVirginia Sandonis Madrid, Spain More articles by this author , Pilar Gonzalez-PeramatoPilar Gonzalez-Peramato Madrid, Spain More articles by this author , Patricia MoyaPatricia Moya Madrid, Spain More articles by this author , Joan PalouJoan Palou Barcelona, Spain More articles by this author , Oscar RodriguezOscar Rodriguez Barcelona, Spain More articles by this author , Ferran AlgabaFerran Algaba Barcelona, Spain More articles by this author , Mercedes RinconMercedes Rincon Burlington, Canada More articles by this author , and Marta Sanchez-CarbayoMarta Sanchez-Carbayo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.746AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Methylation-controlled J protein (MCJ) is a member of the DnaJ family of cochaperones. The DNAJ proteins participate in processes such as protein folding and translocation, cell cycle control by DNA tumor viruses, and regulaton of protein kinases. To our knowledge, MCJ has not been evaluated in bladder cancer to date. In this report we aimed at evaluating the potential relevance of MCJ in bladder cancer progression and in the response to Bacille of Calmette-Guerin therapy in high-risk T1 high grade bladder cancer. METHODS The methylation status of MCJ promoter was evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses in bladder cancer cells (n=14), bladder tumors (n=150), and urinary samples (n=60) of bladder cancer patients and controls. The epigenetic silencing of MCJ by hypermethylation was tested in bladder cancer cells (n=10) before and after azacytidine treatment. MCJ expression patterns were analyzed by immunohistochemistry on tissue arrays containing bladder tumors for which MCJ methylation was assessed. RESULTS MCJ was frequently methylated in bladder cancer cells (86%). MCJ hypermethylation was associated with gene expression, being increased in vitro by azacytidine, a demethylating agent. MCJ was revealed to be frequently methylated in bladder tumors (78%). MCJ methylation was significantly associated with tumor stage (p<0.001) and tumor grade (p<0.05). In a series of patients treated with BCG, the presence of a low MCJ expression alone, or combined with MCJ methylation, were associated with poor BCG response in terms of muscle-invasive progression (p<0.05). Moreover, MCJ methylation in urinary specimens distinguished patients with bladder cancer from controls (p<0.05). CONCLUSIONS MCJ was identified to be epigenetically modified in bladder cancer. MCJ methylation and protein expression patterns associated with cancer progression and clinical outcome and BCG response. Together with its potential to detect bladder cancer patients using urinary specimens suggests further assessment of the utility of MCJ methylation and protein evaluations for the clinical management of patients affected by uroepithelial neoplasias. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e462 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noemi Pompas-Veganzones Madrid, Spain More articles by this author Virginia Sandonis Madrid, Spain More articles by this author Pilar Gonzalez-Peramato Madrid, Spain More articles by this author Patricia Moya Madrid, Spain More articles by this author Joan Palou Barcelona, Spain More articles by this author Oscar Rodriguez Barcelona, Spain More articles by this author Ferran Algaba Barcelona, Spain More articles by this author Mercedes Rincon Burlington, Canada More articles by this author Marta Sanchez-Carbayo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...