肝细胞癌中乳腺癌扩增性抗原1的表达及其对上皮间质转化相关标记分子表达的影响  

Role of amplified in breast cancer 1 in expression of epithelium mesenchymal transition related markers in hepatocellular carcinoma

作　　者：许晶晶[1] 郭思[3] 余海波[4] 刘宇琼[1] 蔡建平[4] 薛瑞[2] 

机构地区：[1]郑州大学第一附属医院病理科,450002 [2]郑州大学第一附属医院重点实验室,450002 [3]河南省人民医院检验科 [4]河南省人民医院肝胆外科

出　　处：《中华肝胆外科杂志》2015年第2期122-127,共6页Chinese Journal of Hepatobiliary Surgery

基　　金：NSFC-河南人才培养联合基金（U1304804）;河南省科技厅基础与前沿技术项目（112300410037）;河南省医学科技攻关项目（201203094）

摘　　要：目的 研究乳腺癌扩增性抗原1（AIB1）、上皮间质转化（EMT）标记分子在肝癌中的表达及其与临床病理特征之间的关系,观察RNA干扰沉默AIB1对HepG2细胞相应EMT标记分子的表达及细胞侵袭能力的影响.方法 用免疫组织化学染色法检测81例肝细胞癌标本中AIB1、EMT标记分子紧密连接蛋白（ZO-1）、上皮样钙黏蛋白（E-cadherin）、波形蛋白（Vimentin）和神经性钙黏蛋白（N-cadherin）的表达,并分析其临床意义.用以AIB1基因为靶点的pLenti6-AIB1 RNAi慢病毒载体感染肝癌细胞HepG2后,检测其AIB1及EMT标记分子mRNA和蛋白水平的表达,用Transwell分析细胞的侵袭能力.结果 肝细胞癌组织中AIB1蛋白表达水平明显高于正常癌旁组织.淋巴结转移性肝细胞癌中AIB1高表达的发生率是63％ （P ＜0.05）.癌组织中AIB1蛋白表达与E-cadherin蛋白呈明显负相关,而与Vimentin蛋白呈正相关.pLenti6-AIB1 RNAi慢病毒载体感染HepG2细胞后,AIB1mRNA和蛋白表达水平显著下降.感染后HepG2细胞侵袭能力明显下降;E-cadherin蛋白表达水平明显上调,Vimentin蛋白表达水平明显下降.结论 AIB1在肝细胞癌中表达增加,且与肝细胞癌侵袭性转移相关.沉默AIB1表达可引起肝癌细胞HepG2中Vimentin表达下降和E-cadherin表达增加,导致细胞侵袭性下降,提示AIB1通过诱导肝癌细胞的EMT过程而促进肝癌发生侵袭性转移.Objective To investigate the expression and clinical features of amplified in breast cancer 1 （AIB1） and epithelial mesenchymal transition （EMT） markers in human hepatocellular carcinoma and to observe the effect of AIB1 silencing by RNA interference （RNAi） on expression of EMT markers and invasiveness of HepG2 cells.Methods In this study,expression of AIB1,E-cadherin,Vimentin,ZO-1,and N-cadherin protein in 81 hepatocellular carcinomas were assessed through immunohistochemistry and clinicopathological significance was analyzed.After the lentiviral vector of AIB1 RNA interference was transfected into HepG2 cells,the expression of AIB1 and EMT markers was detected by real-time PCR and Western blot.The invasion and metastasis was evaluated by Transwell analysis.Results The expression of AIB1 protein was significantly up-regulated in the hepatocellular carcinoma tissue compared to the normal tumor adjacent tissue.The frequency of AIB1 overexpression in hepatocellular carcinomas with lymph node metastasis is 63% （P 〈 0.05）.Correlation analysis demonstrated that the AIB1 protein expression was inversely correlated with E-cadherin,and positively correlated with Vimentin in hepatocellular carcinomas.After transfection with AIB1 targeting siRNA,the expression of AIB1 mRNA and protein decreased significantly （P 〈 0.05）.Knockdown of AIB1 expression increased the expression of E-cadherin and inhibited the expression of Vimentin.In addition,the invasion of HepG2 cells silenced AIB1 were significantly descented.Conclusion Above data suggests that overexpression of AIB1 might promote invasiveness and metastasis of cancer cells through regulation of E-cadherin and Vimentin expression in hepatocellular carcinomas.

关 键 词：乳腺癌扩增性抗原1 上皮间质转化 肝细胞癌 淋巴结转移 

分 类 号：R735.7[医药卫生—肿瘤]