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

Authors

  • F. Lin,

    1. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China
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    • These authors contributed equally to this work.

  • P. Lin,

    1. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China
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    • These authors contributed equally to this work.

  • D. Zhao,

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

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

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

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

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

    1. Department of Urology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
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  • B. Zhao,

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

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

    Corresponding author
    1. Department of Diagnosis, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China
    • Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China
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  • X. Yu

    Corresponding author
    • Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China
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Correspondence: X. Zheng, Department of Diagnosis, Harbin Medical University Cancer Hospital, Harbin Medical University, 150 Haping Road, Harbin 150081, China. Tel./Fax: +86-451-86298218; E-mail: zxl2496@163.com and X. Yu, Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Tel./Fax: +86-451-86671684; E-mail: yxg301@yahoo.com.cn.

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 G1 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.

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