Open AccessS ox2 targets cyclin E , p27 and survivin to regulate androgen‐independent human prostate cancer cell proliferation and apoptosis
Author(s) -
Lin F.,
Lin P.,
Zhao D.,
Chen Y.,
Xiao L.,
Qin W.,
Li D.,
Chen H.,
Zhao B.,
Zou H.,
Zheng X.,
Yu X.
Publication year - 2012
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2012.00812.x
Subject(s) - du145 , survivin , cell growth , cancer research , pi3k/akt/mtor pathway , lncap , cell cycle , biology , sox2 , apoptosis , protein kinase b , cancer cell , microbiology and biotechnology , chemistry , signal transduction , cancer , transcription factor , gene , biochemistry , genetics
Objectives S ox2 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 S ox2 on cell proliferation and apoptosis, and investigated effects of TGF ‐α on expression of S ox2 on androgen‐independent human prostate cancer cells. Materials and methods Expression of S ox2 has been determined by RT ‐ PCR , western blot analysis and immunocytochemistry, using RNA i and over‐expression strategy to study functions of S ox2 in DU 145 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 S ox2 was expressed in six human prostate cancer cell lines, and its inhibition reduced cell proliferation and induced apoptosis in DU 145 cells. We have shown that knock‐down of S ox2 inhibited G 1 to S phase transition concomitantly with down‐regulation of cyclin E and up‐regulation of p27 proteins. Conversely, over‐expression of S ox2 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 S ox2 and survivin protein expression via the EGFR / PI 3 K / AKT pathway. Conclusions S ox2 expression is necessary for cell proliferation and evasion of apoptosis in prostate cancer cells and TGF ‐α could regulate S ox2 and survivin expression by activating the EGFR / PI 3 K / AKT pathway.