中国癌症杂志 ›› 2016, Vol. 26 ›› Issue (12): 968-973.doi: 10.19401/j.cnki.1007-3639.2016.12.002

• 论著 • 上一篇    下一篇

HER-2通过ZEB1促进乳腺癌细胞上皮间质转化

侯 净1,2,任智晶3,魏 娜1,倪 青1,郭小毛2   

  1. 1. 贵州省人民医院乳腺外科,贵州 贵阳 550002 ;
    2. 复旦大学附属肿瘤医院放疗科,复旦大学上海医学院肿瘤学系,上海 200032 ;
    3. 贵州省人民医院检验科,贵州 贵阳 550002
  • 出版日期:2016-12-30 发布日期:2017-01-23
  • 通信作者: 郭小毛 E-mail: guoxm1800@126.com

HER-2 promotes breast cancer cell epithelial-mesenchymal transition by regulating ZEB1

HOU Jing1,2, REN Zhijing3, WEI Na1, NI Qing1, GUO Xiaomao2   

  1. 1. Department of Breast Surgery, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China; 2. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 3. Department of Laboratory, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou Province, China
  • Online:2016-12-30 Published:2017-01-23
  • Contact: GUO Xiaomao E-mail: guoxm1800@126.com

摘要: 背景与目的:人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)是表皮生长因子受体家族中的一员,它参与细胞多个生物过程,如细胞增殖、侵袭和凋亡等。有研究表明,HER-2与细胞上皮间质转化(epithelial-mesenchymal transition,EMT)过程相关,但具体机制有待进一步探讨,本研究旨在探讨HER-2对EMT的调节机制。方法:用Transwell小室模拟细胞的迁徙侵袭能力;采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测目的基因的表达;用活性氧检测试剂盒检测细胞活性氧的水平。结果:Transwell小室模拟实验发现,HER-2过表达能促进乳腺癌细胞的侵袭转移;机制研究表明,HER-2能上调ZEB1,用siRNA降低ZEB1表达使HER-2过表达细胞的侵袭能力受损;此外,HER-2过表达乳腺癌细胞中活性氧水平较低。结论:HER-2可以上调ZEB1的表达而赋予乳腺癌细胞EMT相关特性,ZEB1可作为进一步研究HER-2与EMT调节关系的靶点。

关键词: 乳腺癌, 人类表皮生长因子受体2, ZEB1, 细胞侵袭, 上皮间质转化

Abstract: Background and purpose: Human epidermal growth factor receptor-2 (HER-2), a member of epidermal growth factor receptor family, initiates a diverse set of signaling pathways that ultimately affect such fundamental processes as cell proliferation, cell motility and cell apoptosis. It is reported that HER-2 was associated with epithelial-mesenchymal transition (EMT) process. However, the mechanism needs further investigation. The purpose of this study was to investigate the mechanism of HER-2 on regulating EMT process. Methods: Transwell assay was used to determine the motility of breast cancer cells; Real-time fluorescence quantitative polymerase chain reaction (RTFQ- PCR) was employed to determine the expression of genes of interest, and reactive oxygen species production was measured by reactive oxygen species detection kit. Results: HER-2 overexpression in breast cancer cells could promote cell migration and invasion. Mechanistic study showed that HER-2 overexpression could upregulate ZEB1 expression. ZEB1 silencing by siRNA reduced cell motility of HER-2-overexpressing breast cancer cells. Furthermore, reactive oxygen species produced in HER-2-overexpressing breast cancer cells were less than those produced in corresponding control cells. Conclusion: Our study demonstrated that HER-2 overexpression endowed breast cancer cells with EMT related properties by upregulating ZEB1 expression. ZEB1 could be a candidate target for further study of the relationship between HER-2 and EMT.

Key words: Breast cancer, Human epidermal growth factor receptor-2, ZEB1, Cell invasion, Epithelial-mesenchymal transition