Abstract
Protein tyrosine phosphatase non-receptor type 12 (PTPN12) has been shown to be involved in the development of a number of types of carcinoma. However, the effect of PTPN12 on the proliferation and recurrence of human bladder transitional cell carcinoma (TCC) is unclear. The present study aimed to investigate the expression and function of PTPN12 in human TCC. Samples from 164 patients with TCC, in addition to 146 patients undergoing bladder surgery for indications other than TCC, were examined. PTPN12 protein expression was examined using immunohistochemistry and western blotting, and PTPN12 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. PTPN12 expression was increased following transfection with the PTPN12-expressing, pcDEF3 vector, and PTPN12 expression was decreased by RNA interference, in four TCC cell lines. The proliferation of TCC cells was analyzed by a WST-1 assay and in xenografts on BALB/C nude mice. The effect of PTPN12 on tumor recurrence was analyzed by adhesion, migration and invasion assays in TCC cell lines. PTPN12 expression was significantly decreased in TCC tissues compared with that in normal urothelium, and the level of PTPN12 expression was negatively correlated with tumor size, pathological grade, clinical stage and tumor recurrence. Furthermore, decreased expression of PTPN12 significantly enhanced the proliferation of TCC cells in vitro and in vivo. TCC cells with lower levels of PTPN12 exhibited greater adhesion, migration and invasion. In conclusion, PTPN12 expression is downregulated in human TCC. Restoring PTPN12 activity may represent a novel therapeutic strategy for this disease.