FOXC2调控DLL4/Notch1信号通路对乳腺癌MCF-7细胞血管生成的影响  

Influence of FOXC2 in angiogenesis of breast cancer MCF-7 cells by DLL4/Notch1 signal pathway

作　　者：刘红[1] 谢佳[1] 刘毫[1] 郑曰勇[2] 吴诚义[1] 屈洪波[1] 李聪[3] 

机构地区：[1]重庆医科大学附属第一医院内分泌乳腺外科,重庆400016 [2]重庆医科大学附属第一医院胃肠外科,重庆400016 [3]重庆医科大学附属第一医院妇科,重庆400016

出　　处：《吉林大学学报（医学版）》2014年第3期488-492,I0001,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81100399)

摘　　要：目的:探讨转录因子FOXC2对乳腺癌MCF-7细胞血管生成的影响,阐明FOXC2促进肿瘤血管生成的作用机制。方法:应用FOXC2慢病毒基因转染技术将FOXC2基因和空载体基因分别转染至乳腺癌MCF-7细胞株中,获得稳定转染细胞株;实验分为未转染组、空载体组和过表达组。采用Matrigel基质胶血管形成实验和Transwell小室实验检测各组细胞上清作用下人脐静脉内皮细胞(HUVECs)成管能力和迁移能力,RT-PCR和Western blotting法检测各组细胞中FOXC2、DLL4和Notch1mRNA和蛋白表达。结果:与未转染组和空载体组比较,过表达组MCF-7细胞上清诱导HUVECs闭合小管数和迁移细胞数增加(P<0.05);FOXC2、DLL4和Notch1mRNA和蛋白相对表达水平明显增加(P<0.05)。结论:MCF-7细胞中过表达FOXC2能显著增加HUVECs的成管能力和迁移能力,其机制可能是通过Notch信号通路来实现的。Objective To explore the influence of tranSCription factor FOXC2 in angiogenesis of breast cancer MCF-7 cells and to clarify the action mechanism of FOXC2 in promoting tumor angiogenesis.Methods FOXC2 gene and empty vector gene were transfected into breast cancer of MCF-7 cell line with FOXC2 lentivirus gene transfection technique to obtain stable transfection cell line. The MCF-7 cells were devided into non-transfected group,empty-vector group and over-expression group.Matrigel assay and Transwell chamber test were used to observe the changes of tube formation and migration ability of human umbilical vein endothelial cells （HUVECs）in MCF-7 cells supernatant in various groups. PT-PCR and Western blotting methods were applied to detect the expressions of FOXC2,DLL4 and Notch1 mRNA and protein.Results Compared with non-tranfected group and empty-vector group,the tube formation and the migration number of HUVECs in FOXC2 over-expression group were increased（P〈0.05）;the expressions of FOXC2,DLL4 and Notch1 mRNA and proteins were significantly increased（P〈0.05）.Conclusion The FOXC2 over-expression in MCF-7 cells can increase the tube formation ability and migration ability of HUVECs,and its mechanism may be related to Notch signaling pathway.

关 键 词：乳腺肿瘤 MCF-7 细胞 叉头框-C2 NOTCH信号通路 血管生成 

分 类 号：R733[医药卫生—肿瘤] R737.9[医药卫生—临床医学]