359 ONCOGENIC FUNCTIONS OF SECRETED FRIZZLED-RELATED PROTEIN 2 (SFRP2) IN HUMAN RENAL CANCER

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2010359 ONCOGENIC FUNCTIONS OF SECRETED FRIZZLED-RELATED PROTEIN 2 (SFRP2) IN HUMAN RENAL CANCER Soichiro Yamamura, Kazumori Kawakami, Hiroshi Hirata, Koji Ueno, Sharanjot Saini, Shahana Majid, Peter Carroll, and Rajvir Dahiya Soichiro YamamuraSoichiro Yamamura More articles by this author , Kazumori KawakamiKazumori Kawakami More articles by this author , Hiroshi HirataHiroshi Hirata More articles by this author , Koji UenoKoji Ueno More articles by this author , Sharanjot SainiSharanjot Saini More articles by this author , Shahana MajidShahana Majid More articles by this author , Peter CarrollPeter Carroll More articles by this author , and Rajvir DahiyaRajvir Dahiya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.426AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The secreted Frizzled-related proteins (sFRPs) are modulators of the Wnt signaling pathway which is involved in embryonic development and tumor progression. The functions of secreted frizzled-related protein 2 (sFRP2) have not been studied in renal cancer. Therefore, we investigated the functions of sFRP2 in renal cancer cells. METHODS We studied expression level of sFRP2 using human renal cancer tissue microarray. To study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines which stably expressed sFRP2. To characterize the stable sFRP2 cell lines, we performed assays of in vitro and in vivo cell proliferation, apoptosis, cell cycle, cell invasion and Western blot. RESULTS Human renal cancer tissue microarray revealed that the level of sFRP2 expression was high in normal kidney, low in primary renal cancer tissues and high in metastatic renal cancer tissues, suggesting different roles of the sFRP2 gene in different grades of renal cancer. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to reduce UV-induced apoptosis and increase in the G2 phase of the cell cycle. In the stable sFRP2 cell lines, expression of c-Fos, Bcl2, Bcl-w, cyclinB2 and cyclinE2 genes was significantly increased and p53 expression was decreased. In metastatic Caki1 cells, sFRP2 knockdown inhibited invasion and reduced expression of CD146, MMP2 and Rac1/2/3 genes. This is the first report documenting that sFRP2 modulates proliferation and invasion pathways by altering various genes in renal cancer cells. CONCLUSIONS We found that the level of sFRP2 expression was high in normal kidney, low in primary renal cancer tissues and high in metastatic renal cancer tissues, suggesting different roles in renal cancer. Overexpressed sFRP2 in renal cancer cells promoted cell growth and cell invasion by evoking diverse signalling cascades. This data may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways. San Francisco, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e142 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Soichiro Yamamura More articles by this author Kazumori Kawakami More articles by this author Hiroshi Hirata More articles by this author Koji Ueno More articles by this author Sharanjot Saini More articles by this author Shahana Majid More articles by this author Peter Carroll More articles by this author Rajvir Dahiya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...