吉林大学学报(医学版)

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

刘红1,谢佳1,刘毫1,郑曰勇2,吴诚义1,屈洪波1,李聪3   

  1. (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)
  • 收稿日期:2013-10-28 出版日期:2014-05-28 发布日期:2014-05-28
  • 通讯作者: 吴诚义 E-mail:(Tel: 023-68481463,E-mail: chengyiwu11@163.com)
  • 作者简介:刘 红(1986-),女,贵州省贵阳市人,在读医学硕士,主要从事乳腺癌血管生成的研究。 
  • 基金资助:

    国家自然科学基金资助课题 ( 81100399) 

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

LIU Hong1,XIE Jia1,LIU Hao1,ZHENG Yue-yong2,WU Cheng-yi1,QU Hong-bo1,LI Cong3   

  1. (1.Department of Endocrine  Surgery,First Affiliated Hospital, Chongqing Medical University,Chongqing 400016,China; 2.Department of Gastrointestinal Surgery, First Affiliated Hospital,  Chongqing Medical University,Chongqing 400016,China; 3. Department of Gynaeco
    logy,First Affiliated Hospital, Chongqing Medical University,Chongqing 400016,China)
  • Received:2013-10-28 Online:2014-05-28 Published:2014-05-28

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Notch1 mRNA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Notch1 mRNA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。

关键词: 乳腺肿瘤, MCF-7细胞, 叉头框-C2, Notch信号通路, 血管生成

Abstract:

 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.

Key words: breast neoplasms;MCF-7 cells, forkhead box C-2, Notch signaling pathway, angiogenesis

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