198 EXPRESSION OF SAM POINTED DOMAIN-CONTAINING ETS TRANSCRIPTION FACTOR (SPDEF) ATTENUATES PROSTATE TUMOR METASTASIS

You have accessJournal of UrologyProstate Cancer: Basic Research (I)1 Apr 2013198 EXPRESSION OF SAM POINTED DOMAIN-CONTAINING ETS TRANSCRIPTION FACTOR (SPDEF) ATTENUATES PROSTATE TUMOR METASTASIS Joshua Steffan, Sweaty Koul, and Hari Koul Joshua SteffanJoshua Steffan Aurora, CO More articles by this author , Sweaty KoulSweaty Koul Aurora, CO More articles by this author , and Hari KoulHari Koul Aurora, CO More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1578AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate tumor metastasis is the leading cause of prostate cancer deaths. The transcription factor, SAM Pointed Domain-Containing ETS Factor, (SPDEF), also known as Prostate-Derived ETS Factor (PDEF), is known to regulate multiple prostate metastasis-associated genes. Moreover, SPDEF inversely correlates with a prostate tumor's Gleason Score. Decreased levels of SPDEF promotes increased tumor aggressiveness and metastasis, suggesting that SPDEF may be a tumor metastasis suppressor. As prostate tumor cell lines vary in their expression level of SPDEF protein they serve as a useful model to determine: 1) if differential SPDEF expression affects the metastatic capacity of these cells in mouse models of metastasis and 2) which SPDEF-regulated genes may contribute to metastatic colonization. METHODS Standard in vitro migration, invasion, clonogenic, and RT-PCR assays were performed. In vivo, 1 x 106 LNCaP or PC3 cells were injected subcutaneously or via the tail vein or intra-cardiac route in nude mice. All cells expressed luciferase to monitor metastatic colonization over 12 weeks. RESULTS In vitro we found that increased SPDEF expression decreased tumor aggressiveness. However, although SPDEF expression had no effect on subcutaneous xenograft tumor growth, we demonstrate that increased SPDEF expression in PC3 cells decreased metastatic colonization; whereas SPDEF knockdown in LNCAP cells increased metastatic colonization. In fact, no detectible metastatic colonization was observed in the SPDEF expressing PC3 cells. Lastly, we determined that MMP9 and MMP13 are SPDEF-regulated and involved in prostate tumor cell invasion. CONCLUSIONS These studies demonstrate for the first time that SPDEF expression decreases the metastatic capacity of prostate cancer cells in vivo, while having no effect on subcutaneous tumor cell growth, thus establishing SPDEF as a tumor metastasis suppressor gene. Future studies to determine the mechanism of SPDEF silencing in advanced disease may lead to increased mechanistic insight into the metastatic process and eventually to therapeutic options to either reestablish SPDEF expression or target those SPDEF-regulated gene products involved in prostate tumor metastasis. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e82 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Steffan Aurora, CO More articles by this author Sweaty Koul Aurora, CO More articles by this author Hari Koul Aurora, CO More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...