IFN-γ激活ERK/Jak2-STAT信号通路诱导乳腺癌细胞过表达PD-L1和上皮-间质转化
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金 (No. 31700824) 资助。


IFN-γ induces overexpression of PD-L1 and epithelial- mesenchymal transformation of breast cancer cells through activating ERK/Jak2-STAT signaling pathways
Author:
Affiliation:

Fund Project:

National Natural Science Foundation of China (No. 31700824).

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    旨在探讨IFN-γ诱导乳腺癌细胞株MDA-MB-231表面程序性死亡配体 (PD-L1)的表达、对上皮间质转化的影响及其分子机制。用不同浓度IFN-γ作用MDA-MB-231细胞后,利用蛋白质免疫印迹检测PD-L1、细胞迁移相关蛋白 (E-钙黏蛋白、N-钙黏蛋白、波形蛋白)、ERK、p-ERK、Jak2及p-Jak2的表达水平;通过细胞划痕实验和Transwell实验检测细胞迁移能力;利用免疫荧光实验进一步检测细胞迁移相关蛋白的表达量。结果表明,IFN-γ可上调PD-L1的表达,使细胞划痕融合率显著增高,细胞迁移速率显著加快;波形蛋白和N-钙黏蛋白的表达量升高,E-钙黏蛋白表达量下降;ERK、p-ERK、Jak2及p-Jak2表达水平显著增加。加U0126后PD-L1、ERK及p-ERK表达水平下降,而加入AG490后,PD-L1、Jak2、p-Jak2表达水平下降。结果表明IFN-γ能上调乳腺癌细胞PD-L1表达水平,促进肿瘤细胞迁移,促使细胞从上皮向间质转化,而这一过程可能与ERK及Jak2-STAT信号通路相关。

    Abstract:

    To investigate the effect of INF-γ on the expression of programmed death ligand 1 (PD-L1), epithelial-mesenchymal transition (EMT) and the potential mechanism in breast cancer cell line MDA-MB-231, the cells were treated with different concentrations of INF-γ. The expressions of proteins, including PD-L1, cell-migration-related proteins (E-cadherin, N-cadherin and vimentin), ERK, p-ERK, Jak2, and p-Jak2 were detected by Western blotting analysis and immunofluorescent staining assay. Cell migration was studied through cell wound healing assay and transwell assay. IFN-γ could up-regulate the expressions of PD-L1 in MDA-MB-231 cells. The cell migration rate was significantly increased after adding IFN-γ. The expression levels of vimentin and N-cadherin were increased whereas the expression of E-cadherin was decreased after adding IFN-γ. The expression levels of ERK, p-ERK, Jak2 and p-Jak2 were significantly increased and this phenomenon was inhibited when adding ERK inhibitor U0126 or Jak2 inhibitor AG490. These results demonstrate that IFN-γ could up-regulate the expression of PD-L1, promote cell migration and transmission, and facilitate epithelial-mesenchymal transformation of breast cancer cells and this process may be related with ERK and Jak2-STAT signaling pathways.

    参考文献
    相似文献
    引证文献
引用本文

严玉荣,赵晨辰,杨睿,周婷,许娜. IFN-γ激活ERK/Jak2-STAT信号通路诱导乳腺癌细胞过表达PD-L1和上皮-间质转化[J]. 生物工程学报, 2018, 34(12): 2007-2015

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2018-02-25
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2018-12-24
  • 出版日期:
您是第位访问者
生物工程学报 ® 2024 版权所有

通信地址:中国科学院微生物研究所    邮编:100101

电话:010-64807509   E-mail:cjb@im.ac.cn

技术支持:北京勤云科技发展有限公司