MP23-19 EZH2 CONTRIBUTES TO PROLIFERATION AND METASTASIS IN RENAL CELL CARCINOMA CELLS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2014MP23-19 EZH2 CONTRIBUTES TO PROLIFERATION AND METASTASIS IN RENAL CELL CARCINOMA CELLS Dong Zhang, Xiaojie Yang, Hongliang Li, and Tie Chong Dong ZhangDong Zhang More articles by this author , Xiaojie YangXiaojie Yang More articles by this author , Hongliang LiHongliang Li More articles by this author , and Tie ChongTie Chong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.887AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The enhancer of zest homolog 2 (EZH2) gene has been recognized as a proto-oncogene and linked to human malignancies. Here, we determined potential role of EZH2 in prosurvival and metastasis of renal cell carcinoma (RCC) and its possible mechanisms. METHODS EZH2-overexpressing vector and siRNA for EZH2 were transfected into 786-O and ACHN cells respectively. Growth rate was determined by MTT. Cell cycle was detected by flow cytometry following EZH2 alteration. Wound healing and Transwell assay were used to determine migration and invasive potential in response to EZH2 change. Real-time PCR and Western blot was used to determine alteration of MMPs and TIMPs. RESULTS EZH2 overexpressing promoted cell growth in 786-O cells, whereas EZH2 knockdown inhibit cell growth in ACHN cells. EZH2 stimulated 786-O cells to enter S phase, however, ACHN cells were arrested in G1/S phase following EZH2 knockdown. In addition, EZH2 elevated migration and invasion potential in 786-O cells, and suppress of EZH2 resulted in inhibition of migratory and invasive capability in ACHN cells. Mechanically, EZH2 could repress TIMP-1 activity rather than TIMP-2 or -3, furthermore, inhibition of EZH2 markedly reduced the proteolytic activity of MMP-9, whereas MMP-2 activity was found not to be changed significantly. CONCLUSIONS EZH2 plays a critical role in proliferation in RCC cells. In addition, EZH2 can enhance both migratory and invasive potential of RCC cells in vitro. EZH2 plays an active role in the upregulation of MMP activity, downregulaion of TIMP, and subsequent invasion of RCC cells. Facilitating of invasion makes EZH2 a promising target for management of RCC metastasis. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e250 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Dong Zhang More articles by this author Xiaojie Yang More articles by this author Hongliang Li More articles by this author Tie Chong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...