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Cell Prolif. 2012 Jun;45(3):207-16. doi: 10.1111/j.1365-2184.2012.00812.x. Epub 2012 Apr 2.

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

Author information

1
Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China.

Abstract

OBJECTIVES:

Sox2 is a major transcription factor and the transforming growth factor-α (TGF-α)/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-α 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 over-expression 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 G(1) to S phase transition concomitantly with down-regulation 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 survivin in DU145 cells. We also found that TGF-α up-regulated 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-α could regulate Sox2 and survivin expression by activating the EGFR/PI3K/AKT pathway.

[Indexed for MEDLINE]

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