Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human prostate cancer cell proliferation and apoptosis

Objectives: Sox2 is a major transcription factor and the transforming growth factor- a ( TGF- a)/ EGFR autocrine loop is a hallmark of prostate cancer progression. In this study, we have evaluated the effects and potential mechanisms of Sox2 on cell proliferation and apoptosis, and investigated effects of TGF- a on expression of Sox2 on androgen- independent human prostate cancer cells. Materials and methods: Expression of Sox2 has been determined by RT- PCR, western blot analysis and immunocytochemistry, using RNAi and overexpression strategy to study functions of Sox2 in DU145 and PC- 3 cells. Changes in level of proliferation, cell cycle and apoptosis profiles were measured by MTT, colony- forming, bromodeoxyuridine incorporation assays, cell cycle and annexin V analysis. Results: Sox2 was expressed in six human prostate cancer cell lines, and its inhibition reduced cell proliferation and induced apoptosis in DU145 cells. We have shown that knock- down of Sox2 inhibited G1 to S phase transition concomitantly with downregulation of cyclin E and up- regulation of p27 proteins. Conversely, over- expression of Sox2 led to the opposite effect in PC- 3 cells but its inhibition induced apoptosis by down- regulation of survi- vin in DU145 cells. We also found that TGF- a upregulated Sox2 and survivin protein expression via the EGFR/ PI3K/ AKT pathway. Conclusions: Sox2 expression is necessary for cell proliferation and evasion of apoptosis in prostate cancer cells and TGF- a could regulate Sox2 and survivin expression by activating the EGFR/ PI3K/ AKT pathway.