1148 RETICULOCALBIN-1 DOWN-REGULATION AS A POSSIBLE PREDICTOR OF CISPLATIN RESISTANCE IN UROTHELIAL CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20101148 RETICULOCALBIN-1 DOWN-REGULATION AS A POSSIBLE PREDICTOR OF CISPLATIN RESISTANCE IN UROTHELIAL CANCER Masaaki Tachibana, Yoshio Ohno, Masahiko Kuroda, Ayako Tanaka, Kenji Shimodaira, Jun Nakashima, Takashi Hirano, and Norihiko Ikeda Masaaki TachibanaMasaaki Tachibana More articles by this author , Yoshio OhnoYoshio Ohno More articles by this author , Masahiko KurodaMasahiko Kuroda More articles by this author , Ayako TanakaAyako Tanaka More articles by this author , Kenji ShimodairaKenji Shimodaira More articles by this author , Jun NakashimaJun Nakashima More articles by this author , Takashi HiranoTakashi Hirano More articles by this author , and Norihiko IkedaNorihiko Ikeda More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.647AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cisplatin is a main chemotherapeutic agent for urothelial cancer. Urothelial cancer patients treated with cisplatin-based chemotherapy often develop cisplatin resistance and, consequently, cancer recurrence. Therefore, elucidation of the mechanisms underlying cisplatin-resistance is crucial for efficient cancer chemotherapy. Proteomic analysis of cisplatin-resistant lung cancer cell lines identified reticulocalbin-1 as one of the proteins associated with cisplatin resistance. The purpose of this study is to evaluate significance of reticulocalbin-1 in urothelial cancer. METHODS Cisplatin-resistant sublines were established from the urothelial cancer cell lines KU-1, KU-7, and KU-19-19 by repeated subcultures with increasing cisplatin concentrations. Cell cycle analysis was performed by flow cytometry, and cisplatin cytotoxicity was determined with the Alamar Blue cytotoxicity assay. Reticulocalbin-1 expression was analyzed by real-time reverse transcriptase PCR and western blot. Surgically resected urothelial cancer specimens were immunohistochemically analyzed for reticulocalbin-1 to determine its association with response to cisplatin-based chemotherapy. Reticulocalbin-1 immunostaining was determined by the percentage of reticulocalbin-1-positive cells: weak staining, ≤25% of the tumor cells were positive for reticulocalbin-1; moderate, ≤50%; strong, >90%. RESULTS Cell growth inhibition was 2.5-fold greater in cisplatin-resistant sublines than in the parental cell lines. The S-phase fraction showed a significant increase. Reticulocalbin-1 was down-regulated in all three cisplatin-resistant cell lines as compared with their parent cell lines on both mRNA and protein levels. In immunohistochemical analysis, reticulocalbin-1 was expressed in normal urothelial epithelium. Fifteen tumors were strongly positive for reticulocalbin-1; 18, moderately positive; 20, weakly positive. Seventy-five percent (15/20) of patients with weak positive primary cancer did not respond to the chemotherapy. CONCLUSIONS Reticulocalbin-1 expression may be a marker for response to cisplatin-based chemotherapy in urothelial cancer. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e444 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masaaki Tachibana More articles by this author Yoshio Ohno More articles by this author Masahiko Kuroda More articles by this author Ayako Tanaka More articles by this author Kenji Shimodaira More articles by this author Jun Nakashima More articles by this author Takashi Hirano More articles by this author Norihiko Ikeda More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...