上海交通大学学报(医学版) ›› 2021, Vol. 41 ›› Issue (7): 839-848.doi: 10.3969/j.issn.1674-8115.2021.07.001

• 创新团队成果专栏 •    下一篇

MUC1在HER2阳性乳腺癌发病中的作用及机制研究

王成志(), 邓华云, 庞智, 黄雷()   

  1. 上海交通大学基础医学院组织胚胎学与遗传发育学系,上海 200025
  • 出版日期:2021-07-28 发布日期:2021-08-03
  • 通讯作者: 黄雷 E-mail:1805490350@qq.com;huanglei@shsmu.edu.cn
  • 作者简介:王成志(1994—),男,硕士;电子信箱:1805490350@qq.com
  • 基金资助:
    国家自然科学基金(82073111);上海交通大学医学院高水平地方高校创新团队(SSMU-ZLCX20180102)

Mechanism of MUC1 in the pathogenesis of HER2-positive breast cancer

Cheng-zhi WANG(), Hua-yun DENG, Zhi PANG, Lei HUANG()   

  1. Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
  • Online:2021-07-28 Published:2021-08-03
  • Contact: Lei HUANG E-mail:1805490350@qq.com;huanglei@shsmu.edu.cn
  • Supported by:
    National Nature Science Foundation of China(82073111);Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZLCX20180102)

摘要:

目的·研究黏蛋白1(mucin 1,MUC1)在人类表皮生长因子受体2 (human epidermal growth factor receptor 2,HER2)阳性乳腺癌发病中的作用及其调控的分子机制。方法·使用病毒感染技术构建MT2/MUC1诱导表达细胞株和MT2/Vec及MT2/CD过表达细胞株;采用蛋白质印迹法(Western blotting)检测过表达MUC1和MUC1-CD后6-磷酸葡萄糖脱氢酶 (glucose-6-phosphate 1-dehydrogenase,G6PD)的蛋白质表达水平;通过细胞计数试剂盒8(cell counting kit-8,CCK-8)法、平板克隆形成实验、细胞划痕实验、Transwell迁移实验和肿瘤细胞成球实验,研究MUC1对HER2阳性乳腺癌细胞MT2增殖、克隆形成、迁移和成球的影响;使用GP6D的抑制剂6-AN抑制酶活性,CCK-8检测乳腺癌细胞增殖;采用GEPIA和Kaplan-Meier Plotter数据库分析HER2、MUC1和G6PD在乳腺癌中的表达及其对乳腺癌患者生存期的影响。结果·过表达MUC1或MUC1-CD促进HER2阳性乳腺癌细胞MT2的增殖、克隆形成、迁移和成球,并且提高G6PD的蛋白质表达水平。抑制G6PD活性显著降低MUC1和MUC1-CD诱导的细胞增殖。G6PD蛋白在乳腺癌组织中表达上调且与乳腺癌患者生存期缩短相关。结论·MUC1可能通过调控G6PD的表达促进HER2阳性乳腺癌的进程,提示抑制磷酸戊糖途径可能成为HER2阳性乳腺癌治疗的靶点。

关键词: 乳腺癌, 黏蛋白1, 磷酸戊糖途径, 6-磷酸葡萄糖脱氢酶

Abstract:

Objective·To study the role and mechanism of mucin 1 (MUC1) in the pathogenesis of HER2-positive breast cancer.

Methods·Virus infection technology was employed to construct MT2/MUC1 and MT2/Vec/MUC1-CD overexpression cell lines; Western blotting was used to detect the expression level of relative proteins; the ability of cell proliferation, migration and sphere formation were detected by using cell counting kit-8 (CCK-8), colony formation, wound healing, transwell and sphere formation experiments respectively; inhibitor 6-AN was used to inhibit glucose-6-phosphate 1-dehydrogenase (G6PD) activity, and the proliferation of breast cancer cells was detected by CCK-8. GEPIA and Kaplan-Meier Plotter database were analyzed to figure out the relationship of HER2, MUC1 and G6PD expression with the survival of breast cancer patients.

Results·Overexpression of MUC1 or MUC1-CD promoted the proliferation, clone formation, migration and sphere formation of MT2 HER2-positive breast cancer cells, as well as elevating the protein level of G6PD. Inhibition of G6PD activity significantly reduced cell proliferation induced by MUC1 and MUC1-CD. High level of G6PD protein in breast cancer tissues is associated with significantly lower survival of breast cancer patients.

Conclusion·MUC1 may promote the progression of HER2-positive breast cancer by up-regulating the expression of G6PD, suggesting that inhibition of the pentose phosphate pathway may be a target for the treatment of HER2-positive breast cancer.

Key words: breast cancer, mucin 1 (MUC1), pentose phosphate pathway (PPP), glucose-6-phosphate 1-dehydrogenase (G6PD)

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