MP34-11 MARKEDLY INCREASED OCT-4 AND NANOG EXPRESSION CORRELATES WITH MULTIDURG RESISTANCE (MDR) PROCESS IN BLADDER CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2014MP34-11 MARKEDLY INCREASED OCT-4 AND NANOG EXPRESSION CORRELATES WITH MULTIDURG RESISTANCE (MDR) PROCESS IN BLADDER CARCINOMA Yi Sun, Liang Liang, Yule Chen, Yongyi Cheng, Yonggang Xu, and Dalin He Yi SunYi Sun More articles by this author , Liang LiangLiang Liang More articles by this author , Yule ChenYule Chen More articles by this author , Yongyi ChengYongyi Cheng More articles by this author , Yonggang XuYonggang Xu More articles by this author , and Dalin HeDalin He More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1024AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer (BCa) is the most prevalent and easy recurrent cancer worldwide, high propensity for recurrence and progression are still serious problems leading to high costs and life-treatment. Multidrug resistant always induced metastasis and treatment failure. Cancer stem cells (CSC) model theoretically contribute to BCa metastasis and mulitidrug resistantce. In this study, we screened BCa stemness specific marker and further detected the potential roles during multidrug resistant process. METHODS 65 pairs of primary and relapsed chemo-resistant tumors were collected during past 10 years from shaanxi provincial people¡¯s hospital, differential expression profile of stemness markers (Nanog, Oct4, Bmi1, CD117, CD133, and ABCG2) were screened by IHC staining and qPCR assay. The specific stemness markers were further confirmed with newly constructed multidrug resistant (253J-ADM) and their parental cell by WB, qPCR ,in vitro and in vivo tumorigenesis assay. We finally evaluated the self-renewal ability and chemosensitivity change after knocking down specific markers by siRNA in multidrug resistant BCa cell line. RESULTS Highly expressed the stemness markers (Nanog, Oct4, Bmi1, CD117, CD133, and ABCG2) was detected in relapsed chemo-resistant tumors vs primary tumor (*p<0.05 for Bmi1, CD117, CD133, and ABCG2). Oct4 and Nanog expression was significantly observed in chemo-resistant patients (**p< 0.01), which also showed correlation to prognosis. Similar results obtain by qPCR array. Furthermore, Oct4 and Nanog expression were also upregulated in multidrug resistant (253J-ADM) cell compared with parental cell, the higher tumorigenesis ability were also observed by in vitro and in vivo tumorigenesis assay(*p<0.05). Knocking down of Oct4 or Nanog in multidrug resistant BCa cell line dramatically suppressed cell renew ability (*p<0.05) and enhanced chemosensitivity to chemo-drugs (mitomycin/ pirarubicin) (*p<0.05). CONCLUSIONS These data indicate that cancer stem-like properties were expanded during the acquisition of multidrug resistance in BCa. Clinically, BCa stemness markers (Oct4 and nanog) overexpression may promote the BCa recurrence to resist multidrugs, which could be a potential therapeutic target for chemoresistant BCa treatment. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e365-e366 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Yi Sun More articles by this author Liang Liang More articles by this author Yule Chen More articles by this author Yongyi Cheng More articles by this author Yonggang Xu More articles by this author Dalin He More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...