139 THE STRESS RESPONSE PROTEIN, PROSTATE ASSOCIATED GENE 4, IS ASSOCIATED WITH LESS AGGRESSIVE PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011139 THE STRESS RESPONSE PROTEIN, PROSTATE ASSOCIATED GENE 4, IS ASSOCIATED WITH LESS AGGRESSIVE PROSTATE CANCER Yu Zeng, Takumi Shirashi, John Kim, Steven Mooney, Alan Meeker, Jun Luo, Robert Getzenberg, and Prakash Kulkarni Yu ZengYu Zeng Baltimore, MD More articles by this author , Takumi ShirashiTakumi Shirashi Baltimore, MD More articles by this author , John KimJohn Kim Baltimore, MD More articles by this author , Steven MooneySteven Mooney Baltimore, MD More articles by this author , Alan MeekerAlan Meeker Baltimore, MD More articles by this author , Jun LuoJun Luo Baltimore, MD 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.2011.02.206AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate-Associated Gene 4 (PAGE4) is a member of the Cancer/Testis Antigens (CTAs) that is up-regulated in prostate cancer (PCa) and symptomatic but not asymptomatic benign prostatic hyperplasia (BPH). However, its functional role and biological significance in PCa remain elusive. The goal of this study is to investigate the PAGE4 expression pattern in PCa and its potential relevance to PCa development and progression. METHODS PAGE4 mRNA expression was determined by real-time RT-PCR in the PCa tissue samples obtained from 90 organ-confined tumors and 21 metastatic sites. The relationship between PAGE4 mRNA level and PSA recurrence was evaluated. The mRNA level of PAGE4 in isolated cell types was analyzed in samples obtained from 8 cancer containing prostates and 5 that did not have cancer by laser capture microdissection. Immunohistochemical staining was used to detect PAGE4 protein expression in PCa. Expression of PAGE4 was up-regulated by pCMV-PAGE4-GFP transfection and cell viability was determined using the WST-1 assay. Cell cycle distribution, apoptosis, DNA damage, and cell migration were evaluated. RESULTS PAGE4 mRNA is higher in the adjacent normal region (pathologically normal area from diseased prostate) than in cancer itself. Moreover, the lower mRNA level of PAGE4 in cancer tissues is correlated with higher tumor recurrence and lower PSA-free survival in patients with organ-confined PCa. Immunohistochemistry revealed that PAGE4 was highly expressed in the epithelial cells associated with infiltrating inflammatory cells, namely proliferative inflammatory atrophy, which is recognized as a precursor of PCa. Furthermore, in PCa tissues, the mRNA level of PAGE4 is positively associated with that of Glutathione S-transferase P1, which is a stress response gene protecting PCa development. In PCa cells, PAGE4 is induced by various stress factors including treatment with the proinflammatory cytokine TNF-α. Over-expression of PAGE4 favored cell survival under stress stimulation, such as glucose-deprivation and chemical drug treatment, and also decreased PCa cell migration. CONCLUSIONS These data suggest that PAGE4 appears to represent an atypical CTA that is up-regulated in the diseased prostate and may be associated with less aggressive PCa. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e59 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yu Zeng Baltimore, MD More articles by this author Takumi Shirashi Baltimore, MD More articles by this author John Kim Baltimore, MD More articles by this author Steven Mooney Baltimore, MD More articles by this author Alan Meeker Baltimore, MD More articles by this author Jun Luo Baltimore, MD 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 ...