Mp85-01 myocyte enhancer factor 2a (mef2a) is up-regulated in clear cell renal cell carcinoma

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2016MP85-01 MYOCYTE ENHANCER FACTOR 2A (MEF2A) IS UP-REGULATED IN CLEAR CELL RENAL CELL CARCINOMA Adam Kinnaird, Bruno Saleme, Vikram Gurtu, Sotirios Zervopoulos, Aristeidis Boukouris, Alois Haromy, Trevor Stenson, Kristalee Watson, Peter Dromparis, and Evangelos Michelakis Adam KinnairdAdam Kinnaird More articles by this author , Bruno SalemeBruno Saleme More articles by this author , Vikram GurtuVikram Gurtu More articles by this author , Sotirios ZervopoulosSotirios Zervopoulos More articles by this author , Aristeidis BoukourisAristeidis Boukouris More articles by this author , Alois HaromyAlois Haromy More articles by this author , Trevor StensonTrevor Stenson More articles by this author , Kristalee WatsonKristalee Watson More articles by this author , Peter DromparisPeter Dromparis More articles by this author , and Evangelos MichelakisEvangelos Michelakis More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2267AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mef2A is a master transcription factor involved in cellular metabolism, epithelial-mesenchymal transition and invasion. Normally expressed at high levels in heart and skeletal muscle, it has recently been identified in leukemia, breast and hepatocellular carcinomas. As a tumor with significant metabolic derangement, we hypothesized that Mef2A is up-regulated in ccRCC, where it promotes tumor growth, migration and invasion. METHODS Fluorescent immunohistochemistry was performed on normal kidney and RCC tissues collected from patients undergoing radical nephrectomy. A Mef2 dual luciferase reporter assay measured Mef2 transcriptional activity. Transient and long-term knockdown of Mef2A with siRNA and shRNA was induced in human RCC cells, which were then used in vitro and in a xenotransplant model of nude mice, respectively. Primeview Affymetrix gene chips and standard qRT-PCR identified and confirmed differentially expressed genes, respectively. A CCL20 ELISA measured concentration of CCL20 in RCC supernatant. Standard scratch and commercially available invasion assays were used. RESULTS Patient RCC tissues express significantly higher levels of Mef2A compared to normal kidney tissues taken from the same patients, n=52 (p<0.001). Mef2 transcriptional activity was significantly elevated in RCC vs. proximal tubule cells (p<0.01). Gene chip analysis shows CCL20 (a chemokine involved in tumor migration and invasion) to be the most altered target in RCC cells treated with siMef2A. Knockdown of Mef2A reduced CCL20 mRNA >6 fold as well as the concentration of CCL20 in the supernatant of RCC cells (p<0.05). Knockdown of Mef2A reduced tumor cell migration and invasion (p<0.01, respectively). After one month, shMef2A tumor xenografts were significantly smaller compared to the shScr (scrambled shRNA) control tumors (p<0.01). CONCLUSIONS Mef2A is up-regulated in human RCC compared to normal kidney from the same patients. Inhibition of Mef2A inhibits tumor cell migration and invasion as well as reduces tumor size, opening the potential of a new therapeutic target to advanced RCC, a tumor that remains fatal. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1098 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Adam Kinnaird More articles by this author Bruno Saleme More articles by this author Vikram Gurtu More articles by this author Sotirios Zervopoulos More articles by this author Aristeidis Boukouris More articles by this author Alois Haromy More articles by this author Trevor Stenson More articles by this author Kristalee Watson More articles by this author Peter Dromparis More articles by this author Evangelos Michelakis More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...