title: Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human prostate cancer cell proliferation and apoptosis.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, Harbin, China.
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: W
authors.initials: W
authors.lastname: Qin
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Zou
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.forename: X
authors.initials: X
authors.lastname: Yu
mesh_terms: D000728:Androgens / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019927:Cyclin E / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000728:Androgens; C107489:BIRC5 protein, human; D019927:Cyclin E; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D000077022:Survivin; D016211:Transforming Growth Factor alpha; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt