PAX-6在人乳腺癌中的表达及促进肿瘤转移的机制  

Expression of PAX-6 in human breast cancer and its mechanism of promoting tumor metastasision

作　　者：黄炜 陈世满 李雅琼 李金友 汪令成 Huang Wei;Chen Shiman;Li Yaqiong;Li Jinyou;Wang Lingcheng(Department of Thyroidectomy and Vascular Surgery,Renmin Hospital,Hubei University of Medicine,Hubei Shiyan 442000,China)

机构地区：[1]湖北医药学院附属人民医院甲状腺乳腺血管外科

出　　处：《现代肿瘤医学》2019年第19期3397-3402,共6页Journal of Modern Oncology

摘　　要：目的:研究配对盒基因-6(paired box,Pax-6)在人乳腺癌组织中的表达和临床预后,及PAX-6对乳腺癌细胞MB-231和MCF-7迁移和侵袭的影响及机制。方法:以人正常乳腺上皮、乳腺癌及配对癌旁组织为研究对象;通过实时定量PCR和免疫蛋白印迹实验分析PAX-6在乳腺癌组织、癌旁组织及正常上皮组织中的相对表达;在线数据库分析PAX-6在乳腺癌中表达与预后的相关性;免疫蛋白印迹实验分析PAX-6在乳腺癌细胞系中的相对表达,选取高表达PAX-6基因的乳腺癌MB-231和MCF7细胞进行基因敲除,设定敲除效率高的si-PAX-6(#1)为实验组(P<0.05),si-NC细胞为对照组;Transwell实验分析PAX-6敲除对细胞迁移和侵袭的影响;实时定量PCR和免疫蛋白印迹实验验证PAX-6基因对细胞迁移和侵袭影响的机制。结果:与正常乳腺上皮、配对癌旁组织相比,PAX-6在人乳腺癌组织中表达上调(P<0.001);在线数据发现PAX-6的表达程度与乳腺癌的预后呈负相关,PAX-6基因表达程度越高,患者预后越差(P=0.038);与正常乳腺上皮细胞相比,PAX-6基因在乳腺癌细胞MB231、MCF-7和BT-549中高表达;与对照组相比,实验组si-PAX-6(#1)细胞迁移和侵袭明显受到抑制(P<0.001);si-PAX-6(#1)敲除后能下调Vimentin、N-cadherin、MMP2、MMP7和MMP9 mRNA和蛋白表达水平,上调E-cadherin mRNA和蛋白表达水平。结论:PAX-6在乳腺癌的发生发展中起着重要的作用,可能作为潜在的癌基因参与乳腺癌的进程。Objective:To investigate the expression and the clinical significance of PAX-6 in human breast cancer,and the effects of PAX-6 on migration and invasion of breast cancer cell lines MB-231 and MCF-7.Methods:qRT-PCR and Western blot were used to analyse the relative expression of PAX-6 in human normal breast tissues,breast cancer tumors and paired surgical margin tissues.PAX-6 expression and prognostic analyses were analysed through online database.Western blot was used to analyse the relative expression of PAX-6 in breast cancer cell lines.The si-NC was set as control group,and the si-PAX-6(#1) was the experimental group,to investigate the migration and invasion of malignant function of PAX-6 in breast cancer cell lines.We used transwell experiment to analyse the ability of cell migration and invasion.qRT-PCR and Western blot were used to analyse the basic mechanism.Results:PAX-6 expression were significantly up-regulated in breast cancer tissues compared to normal breast tissues and surgical margin tissues ( P <0.001),also prognostic analyses showed that higher levels of PAX-6 expression could have a worse survival rate ( P =0.038).And Western blot assay showed that PAX-6 were significantly up-regulated in breast cancer cell lines MB-231,MCF-7 and BT-549 compared with normal MCF-10A.Transwell assay showed that si-PAX-6(#1) in MB-231 and MCF-7 cell lines resulted in a significant decrease in migration and invasion cell than control group.Furthermore,the expressions of E-cadherin were significantly up-regulated,and the expressions of Vimentin,N-cadherin,MMP2,MMP7 and MMP9 were down-regulated in MB-231 and MCF7 cells.Conclusion:PAX-6 expression is up-regulated in human breast cancer,and appearred to be a functional oncogene regulating tumorigenesis of breast cancer.

关 键 词：乳腺癌 PAX-6 癌基因 转移 

分 类 号：R737.9[医药卫生—肿瘤]