孙 盈,杨 锋,夏靖华.HIP1影响食管鳞癌Akt/GSK3β信号通路及EMT相关蛋白表达分析[J].肿瘤学杂志,2020,26(5):407-412.
HIP1影响食管鳞癌Akt/GSK3β信号通路及EMT相关蛋白表达分析
Effect of HIP1 on Expression of EMT-related Proteins in Esophageal Squamous Cell Carcinoma Through Akt/GSK3β Signaling Pathway
投稿时间:2019-09-17  
DOI:10.11735/j.issn.1671-170X.2020.05.B008
中文关键词:  亨廷顿蛋白相互作用蛋白1  上皮间充质转化  食管鳞癌
英文关键词:huntingtin interacting protein 1  epithelial mesenchymal transformation  esophageal squamous cell carcinomas
基金项目:
作者单位
孙 盈 空军军医大学第二附属医院 
杨 锋 空军军医大学第二附属医院 
夏靖华 空军军医大学第二附属医院 
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中文摘要:
      摘 要:[目的] 探讨亨廷顿蛋白相互作用蛋白1(huntingtin interacting protein 1,HIP1)促进食管鳞癌转移的作用及机制。[方法]采用qRT-PCR及Western blot检测Akt抑制剂处理HIP1高或低表达食管鳞癌细胞系中HIP1、GSK3β及EMT标志性分子E-cadherin和Vimentin的表达。采用IHC检测食管鳞癌组织样本中目的分子的表达,并分析其表达相关性。[结果] qRT-PCR和Western blot结果显示:与对照组、shRNA-对照组相比,shRNA-HIP1组细胞中Akt、GSK3β及Vimentin基因和蛋白表达显著降低(P<0.001),E-cadherin基因和蛋白表达显著升高(P<0.001);与对照组、OE-对照组相比,OE-HIP1组细胞中Akt、GSK3β及Vimentin基因和蛋白表达显著升高(P<0.001),E-cadherin基因和蛋白表达显著降低(P<0.001)。IHC及相关性分析结果显示,HIP1与GSK3β、Vimentin表达呈正相关(r=0.336,P<0.001;r=0.561,P<0.001),与E-Cadherin表达呈负相关(r=-0.169,P=0.027);GSK3β与Vimentin表达呈正相关(r=0.317,P<0.001),与E-Cadherin表达呈负相关(r=-0.171,P=0.025)。Akt抑制剂处理HIP1高或低表达食管鳞癌细胞系结果显示,Akt抑制剂处理后E-cadherin表达升高,GSK3β及Vimentin表达降低。[结论]HIP1 可能通过激活Akt/GSK3β信号通路促进食管鳞癌EMT的发生。
英文摘要:
      Abstract:[Objective] To investigate the effect of huntingtin interacting protein 1(HIP1) on epithelial-mesenchymal transition(EMT) related proteins in esophageal squamous cell carcinomas(ESCC) and its mechanism. [Methods] The protein expressions of HIP1,GSK3β,EMT related molecules E-cadherin and Vimentin in cancer tissue samples from 173 ESCC patients were detected by immunohistochemistry(IHC). The mRNA and protein expressions of above indicators were also detected by qRT-PCR and Western blot in ESCC cell lines EC109 and Kyse30,respectively. [Results] IHC and correlation analysis showed that HIP1 expression was positively correlated with GSK3βand Vimentin(r=0.336,P<0.001;r=0.561,P<0.001),and was negatively correlated with E-cadherin expression(r=-0.169,P=0.027).GSK3βexpression was positively correlated with Vimentin expression(r=0.317,P<0.001) and negatively correlated with E-cadherin expression(r=-0.171,P=0.025). The qRT-PCR and Western blot showed that,compared with the control group and the shRNA-control group,the mRNA and protein expressions of Akt,GSK3β and Vimentin in the shRNA-HIP1 group were significantly decreased(P<0.001),while the expression of E-cadherin was significantly increased(P<0.001).Compared with control group and OE-control group,the mRNA and protein expressions of Akt,GSK3β,and Vimentin in OE-HIP1 group were significantly increased(P<0.001),while the expression of E-cadherin were significantly decreased(P<0.001). The expression of E-cadherin was increased,while the expression of GSK3β and Vimentin was decreased in EC109 and Kyse30 cells treated with Akt inhibitor. [Conclusion] HIP1 may promote EMT through activation of Akt/GSK3β signaling pathway in ESCC.
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