398 EXPRESSION OF RICTOR IS ASSOCIATED WITH METASTASIS AND POOR PROGNOSIS OF RENAL CELL CARCINOMA

Abstract

INTRODUCTION AND OBJECTIVES: Rictor is a key member of mTORC2, which is crucial to various carcinoma. We measured Rictor expression levels in tumor tissues and six RCC cell lines and evaluated its significance and prognostic use in renal cell carcinoma (RCC). Then we evaluated the change of cell migration, invation and adhesion in RCC cell with downregulation of Rictor. METHODS: Expression of Rictor was examined through immunohistochemistry in a tissue microarray constructed from 217 renal cancer patients to assess the correlation between Rictor expression level and RCC progression. We subsequently analyzed Rictor expression levels in several RCC cell lines through western blotting. Rictor expression in ACHN cell line was down-regulated by SiRNA and the change of cell migration, invision and adhesion wan examined. RESULTS: Rictor positive staining was noted in 74% of RCC patients with 86% in CCRCC and 62 % in PRCC respectively, whereas staining of Rictor expression was remarkably weak in most normal tubules.(FigA). Further statistical analysis showed that Rictor expression was detected in 24 out of 31 long metastasis cases (p 0.000) and in 10 out of 14 lymph node metastasis cases (p 0.003) (Table1). Rictor expression is significantly higher in RCC cell lines with high metastatic potential (ACHN°¢SN12C°¢HTB47) than in primary RCC cell lines(786-O and 769-P )(Fig2A). The Rictor expression level was significantly higher in cases with a symptomatic presentation,as well as in higher TNM stage and higher Furhman grade compared with those with lower stage and lower grade. (Table1) Patients with positive Rictor expression showed lower probability of disease-free survival compared with patients with negative Rictor expression. Knockdown of Rictor by small interference RNA inhibits cancer cell migration and invision and impaired EGF-induced cell adhesion. CONCLUSIONS: The Rictor expression may correlate with cancer migration and metastasis, and the detection of expression levels provides useful prognostic information for cancer-specific survival in patients with RCC. Down-regulation of Rictor inhibits cancer cell migration and invision impaired EGF-induced cell adhesion,so Rictor is a potential target for the treatment of RCC metastasis.