TET1-CD对乳腺癌细胞MDA-MB-231增殖和迁移的影响及其作用机制  

Effect of TET1-CD on proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism

作　　者：赵全华 王申森 马羚[1] 周志祥[1] 黄映辉[1] ZHAO Quanhua;WANG Shensen;MA Ling;ZHOU Zhixiang;HUANG Yinghui(College of Life Sciences and Bioengineering, Beijing University of Technology, Beijing 100124, China)

机构地区：[1]北京工业大学生命科学与生物工程学院

出　　处：《中国肿瘤生物治疗杂志》2019年第6期644-649,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金资助项目(No.21677006);北京市科委基金资助项目(No.K2015311201501)~~

摘　　要：目的:探讨TET1催化结构域(TET1-CD)基因高表达对乳腺癌细胞MDA-MB-231增殖、迁移的影响及其可能的作用机制。方法:慢病毒感染建立高表达TET1-CD的MDA-MB-231细胞系,用qPCR检测细胞中TET1-CD mRNA的表达,Transwell实验和细胞划痕实验检测细胞的迁移能力,MTT法和克隆形成实验检测细胞的增殖能力,WB实验检测MDA-MB-231细胞上皮间质转化(EMT)途径相关蛋白E-cadherin、Vimentin、MMP2以及Wnt、Hedgehog(HH)通路相关蛋白的表达水平。结果:过表达TET1-CD提高乳腺癌MDA-MB-231细胞TET1-CD的表达水平(P<0.01),明显抑制MDA-MB-231细胞的增殖和迁移能力(均P<0.01)。过表达TET1-CD可使乳腺癌MDA-MB-231细胞E-cadherin表达上升,Vimentin、MMP2表达下调(均P<0.05);可使β-catenin、C-myc、CyclinD1、Gli1蛋白表达水平降低(均P<0.05)。结论:过表达TET1-CD可能通过Wnt、HH信号通路抑制EMT途径进而抑制乳腺癌细胞MDA-MB-231的增殖和迁移。Objective: To investigate the effect of high expression of TET1 catalytic domain(TET1-CD) gene on the proliferation and migration of breast cancer MDA-MB-231 cells and its underlying mechanism. Methods: MDA-MB-231 cell line with high TET1-CD expression was established by lentiviral transfection. Real-time quantitative PCR was used to detect the m RNA expression of TET1-CD.Transwell assay and cell scratch assay were used to detect cell migration ability, MTT assay and colony formation assay were used to detect cell proliferation capacity. And WB was adopted to detect the expressions of EMT-related proteins(E-cadherin, Vimentin, MMP2)and Wnt, Hedgehog pathway-related proteins in MDA-MB-231 cells. Results: The MDA-MB-231 cell line with high TET1-CD expression was successfully constructed(all P<0.01). TET1-CD over-expression significantly inhibited the proliferation and migration of breast cancer MDA-MB-231 cells(P<0.01);in addition, TET1-CD over-expression increased the expression of E-cadherin, but down-regulated the expressions of Vimentin, MMP2,β-catenin, Gli1, C-myc and Cyclin D1(all P<0.05). Conclusion: TET1-CD may inhibit the proliferation and migration of breast cancer MDA-MB-231 cells by inhibiting the EMT through Wnt and HH signaling pathway.

关 键 词：乳腺癌 MDA-MB-231细胞 TET1催化结构域 表观遗传 增殖 迁移 上皮间质转化 

分 类 号：R392.12[医药卫生—免疫学] R737.9[医药卫生—基础医学]