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) PDF全文下载地址:
点我下载PDF 