Prolyl isomerase Pin1 promotes tumorigenesis by enhancing ATF1 transcription activity in nasopharyng

来源 :中国病理生理学会第十四届肿瘤专业委员会、第十五届免疫专业委员会联合学术会议 | 被引量 : 0次 | 上传用户:huangsheng200888
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  Objective: Prolyl isomerase Pin1 and activating transcription factor 1 (ATF1) play important roles in cancer.However,their functions in nasopharyngeal carcinoma (NPC) were unclear till now.This study was to find out the relationship between Pin1 and ATF1,and their roles in NPC development.Methods: We characterized and identified a promotive function of Pin1 and ATF1 in NPC with CCK-8,colony formation,immunohistochemistry assay and cell cycle analysis.The relationship between Pin1 and ATF1 was demonstrated with mammalian two-hybrid,GST-pulldown,laser confocal microscopy and coimmunoprecipitation.Results:We firstly found that both Pin1 and ATF1 were highly expressed and positively correlated in NPC tissues but not in normal nasopharyngeal tissues using immunohistochemistry assay.The promoting roles of Pin1 in NPC cell growth and transformation were explored with CCK-8 and colony formation assay in vitro by up-regulation,down-regulation or inhibitor of Pin1.Cell cycle arrest at G1-S-phase was retarded by Pin1 in NPC.The effect of Pin1 on NPC progression was found to be associated with ATF1.Co-expression with ATF1 enhanced the NPC cell transformation ability of Pin1 with colony formation assay.ATF1 transcrpfion activity of Bcl2 and Fra1 was regulated by Pin1 using luciferase reporter assays.Pin1 affected the ATF1 status at protein level but not mRNA level.Pin1 was identified as a new regulator of ATF1 in this study.Mammalian two-hybrid and GST-pulldown assay demonstrated Pin1 interacted with ATF1 exogenously.The endogenous interaction between Pin 1 and ATF1 in NPC cells was confirmed by laser confocal microscopy and coimmunoprecipitation.Moreover,the ATF1 phosphorylation sites at Ser63 or Thr184 mutants abrogated the ATF1 interaction with Pin1 in coimmunoprecipitation experiment results.Conclusions: All our results identified Pin1 as a new regulator of ATF1 transcription activity and thereby promoted tumorigenesis in NPC.
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