Protein tyrosine phosphatase nonreceptor type 12 suppresses the proliferation of renal cell carcinoma by inhibiting the activity of the PI3K/mTOR pathway.

PURPOSE To determine the expression and functions of protein tyrosine phosphatase nonreceptor type 12 (PTPN12) in renal cell carcinoma (RCC). METHODS All RCC tissue and corresponding normal kidney tissue from 116 RCC patients undergoing radical nephrectomy were examined. PTPN12 expression was detected by immunohistochemistry, and PTPN12 mRNA expression by real-time polymerase chain reaction (RT-PCR). PTPN12 expression was increased by stable transfection with a pcDEF3 vector containing full-length cDNA of PTPN12 and was decreased by RNAi in 4 RCC cell lines. Proliferative analysis of RCC cells was done using a WST-1 assay and animal xenograft study. RESULTS PTPN12 expression in RCC tissue was significantly decreased compared with normal kidney tissue, and was overexpressed in larger tumors, metastasis, and high pathological grades. CONCLUSIONS PTPN12 expression decreases in human RCC, it is involved in progression and metastasis, and is an independent prognostic factor in RCC. Restoring PTPN12 activity could be a new therapeutic approach in advanced RCC.