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Objective To explore the mechanism by which Pim-2 signal pathway inhibits apoptosis of prostate cancer cells. Methods We examined the expression levels of Pim-2 and the downstream factors in prostate cancer tissues, benign prostatic hyperplasia tissues, prostate cancer cell lines and prostatic epithelial cells. In prostate cancer DU-145 cell line with Pim-2 or XIAP silencing using RNA interference technique and in non-neoplastic prostatic epithelial cell line RWPE-1 over-expressing Pim-2 or XIAP via gene transfection, we detected the phosphorylation level of eIF4B and the expression of XIAP and examined the apoptosis rate of the cells. Results Pim-2 was significantly over-expressed in prostate cancer tissues and prostate cancer cell lines as compared with benign prostatic hyperplasia tissue and non-neoplastic prostatic epithelial cells. RWPE-1 cells over-expressing Pim-2 showed significantly increased phosphorylation level of eIF4B with enhanced XIAP expression and a significantly lowered apoptosis rate. DU-145 cells with Pim-2 silencing exhibited significantly lowered phosphorylation level of eIF4B and XIAP expression with obviously increased cell apoptosis rate. XIAP silencing in DU-145 cells that over-expressed Pim-2 and XIAP caused a significant increase in the cell apoptosis rate; XIAP over-expression in RWPE-1 cells with low expressions of Pim-2 and XIAP did not cause significant changes in the cell apoptosis rate. Conclusion Pim-2 is over-expressed in prostate cancer cells. Pim-2 may inhibit the apoptosis of prostate cancer cells through phosphorylating eIF4B to promote XIAP expression, and this inhibitory effect occurs only when both Pim-2 and XIAP are over-expressed in prostate cancer cells.