433 SPERM ASSOCIATED ANTIGEN 4 IS A NOVEL BIOMARKER FOR RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research III1 Apr 2012433 SPERM ASSOCIATED ANTIGEN 4 IS A NOVEL BIOMARKER FOR RENAL CELL CARCINOMA Takumi Shiraishi, Naoki Terada, Yu Zeng, Steven Mooney, Sayuri Takahashi, Natsuki Takaha, Tsuneharu Miki, Robert Getzenberg, and Prakash Kulkarni Takumi ShiraishiTakumi Shiraishi Baltimore, MD More articles by this author , Naoki TeradaNaoki Terada Baltimore, MD More articles by this author , Yu ZengYu Zeng Baltimore, MD More articles by this author , Steven MooneySteven Mooney Baltimore, MD More articles by this author , Sayuri TakahashiSayuri Takahashi Baltimore, MD More articles by this author , Natsuki TakahaNatsuki Takaha Kyoto, Japan More articles by this author , Tsuneharu MikiTsuneharu Miki Kyoto, Japan More articles by this author , Robert GetzenbergRobert Getzenberg Baltimore, MD More articles by this author , and Prakash KulkarniPrakash Kulkarni Baltimore, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.500AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Loss of the von Hippel-Lindau (VHL) tumor suppressor gene is associated with a variety of proliferative disorders, especially renal cell carcinoma (RCC). In the absence of pVHL, hypoxia inducible factor α (HIFα) is stabilized under normoxic conditions and stimulates the expression of several genes associated with the survival of cancer cells and tumorigenesis. The Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs have the potential to serve as unique biomarkers and therapeutic targets for cancer. In the present study, we investigated the association between the VHL-mediated gene pathway and the panel of CTAs expression. METHODS RCC4-EV (VHL null) and RCC4-VHL (restored wild type VHL) cells were used to identify CTAs which was associated with the VHL-mediated gene pathway. Deferoxamine mesylate (DFO) was used to mimic hypoxic conditions. The expression of sperm associated antigen 4 (SPAG4) was measured by quantitative real-time PCR using cancer and adjacent normal tissues obtained from 35 patients with RCC. RESULTS SPAG4 was dramatically down-regulated in RCC4-VHL cells compared to RCC4-EV cells. SPAG4 mRNA expression was induced by DFO and this induction was blocked by the knockdown of HIF1α in renal cancer cells expressing both wild type HIF1α and HIF2α. On the other hand, HIF2α played a predominant role in SPAG4 expression in HIF1α defective renal cancer cells. Over-expression of SPAG4 had no effect on cell growth but significantly increased invasion ability using a Matrigel invasion assay. Quantitative real time PCR showed that SPAG4 mRNA expression in cancer specimens from RCC patients was an average 15 times higher than adjacent normal kidney tissues from same patients. Furthermore, the SPAG4 mRNA expression was inversely correlated with tumor size, grade and stage. CONCLUSIONS These results indicate that SPAG4 mRNA expression could serve as a promising diagnostic and prognostic biomarker for RCC. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e177-e178 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takumi Shiraishi Baltimore, MD More articles by this author Naoki Terada Baltimore, MD More articles by this author Yu Zeng Baltimore, MD More articles by this author Steven Mooney Baltimore, MD More articles by this author Sayuri Takahashi Baltimore, MD More articles by this author Natsuki Takaha Kyoto, Japan More articles by this author Tsuneharu Miki Kyoto, Japan More articles by this author Robert Getzenberg Baltimore, MD More articles by this author Prakash Kulkarni Baltimore, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...