MP29-10 TRIM36, A NOVEL ANDROGEN-RESPONSIVE GENE, ENHANCES ANTI-ANDROGEN EFFICACY AGAINST PROSTATE CANCER BY INHIBITING MAPK/ERK SIGNALING PATHWAYS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I1 Apr 2018MP29-10 TRIM36, A NOVEL ANDROGEN-RESPONSIVE GENE, ENHANCES ANTI-ANDROGEN EFFICACY AGAINST PROSTATE CANCER BY INHIBITING MAPK/ERK SIGNALING PATHWAYS Jie Li, Chao Liang, Shangqian Wang, Bianjiang Liu, Gong Cheng, Chao Qin, Pengfei Shao, and Zengjun Wang Jie LiJie Li More articles by this author , Chao LiangChao Liang More articles by this author , Shangqian WangShangqian Wang More articles by this author , Bianjiang LiuBianjiang Liu More articles by this author , Gong ChengGong Cheng More articles by this author , Chao QinChao Qin More articles by this author , Pengfei ShaoPengfei Shao More articles by this author , and Zengjun WangZengjun Wang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.930AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Hormone therapy drugs, such as bicalutamide and enzalutamide, directed against prostate cancer focus on androgen receptor (AR) signaling and are initially effective, but the disease progresses to lethality as resistance to these drugs develops. A method to prolong the drug response time and improve the drug efficacy is still unavailable. In this study, we investigated the functional analysis and androgen regulation of TRIM36 and its underlying mechanisms enhancing anti-androgen efficacy against prostate cancer (PCa). METHODS TRIM36 expression has been detected by mRNA microarray analysis, quantitative reverse transcription (qRT-PCR), Western blotting and Liquid chromatography-Mass Spectrum (LC-MS/MS) in matched prostate cancer and adjacent normal tissues, and prostate cell lines RWPE-1, C4-2, LNCaP, DU145, PC3. A total of 95 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for TRIM36 and androgen receptor (AR) protein expression. Prostate cancer cells stably expressing and shRNAs knockdown TRIM36 were used for CCK-8 assay, clone formation assay and xenograft with or without ADT drugs. Androgen regulation was examined by ChIP, dual-luciferase reporter assay, qRT-PCR and Western blot analysis. RESULTS In this study, we found that 63.4% (64/95) of PCa in TMA expressed the TRIM36 protein. Interestingly, patients with negative TRIM36 expression had a shorter biochemical recurrence-free survival. TRIM36 expression was significantly associated with the Gleason score (P=0.005), delayed prostate cancer cell cycle progression and inhibited cell proliferation in vitro and in vivo, and these effects were mediated via inhibition of the MAPK/ERK phosphorylation pathway. Remarkably, we found that rescuing the expression of TRIM36 during anti-androgen therapy could improve the drug efficacy. CONCLUSIONS Collectively, TRIM36 is a novel androgen-responsive gene, and it dramatically enhanced the efficacy of anti-androgen drugs against prostate cancer. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e369 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jie Li More articles by this author Chao Liang More articles by this author Shangqian Wang More articles by this author Bianjiang Liu More articles by this author Gong Cheng More articles by this author Chao Qin More articles by this author Pengfei Shao More articles by this author Zengjun Wang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...