Document Detail


Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human prostate cancer cell proliferation and apoptosis.
MedLine Citation:
PMID:  22469032     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
F Lin; P Lin; D Zhao; Y Chen; L Xiao; W Qin; D Li; H Chen; B Zhao; H Zou; X Zheng; X Yu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-2
Journal Detail:
Title:  Cell proliferation     Volume:  -     ISSN:  1365-2184     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China.
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