情志应激激素受体调控Yes相关蛋白1影响乳腺癌细胞上皮间充质转化进程研究

The Emotional Stress Hormone Receptor GR Regulates the EMT Process of Breast Cancer Cells by Regulating YAP1

目的:探究情志应激激素受体(GR)与Yes相关蛋白1(YAP1)对乳腺癌MCF-7细胞转移的调控机制,以期为乳腺癌的治疗提供新思路。方法:通过免疫组化实验分析乳腺癌组织和癌旁组织GR和YAP1的表达;将MCF-7细胞分为:si NC组、si GR组和si YAP1组,分别通过MTT实验、Transwell实验、细胞划痕实验和流式细胞术分析MCF-7细胞的增殖、侵袭、迁移能力及凋亡率,通过蛋白免疫印迹实验分析细胞GR和YAP1的表达水平。结果:与癌旁正常组织比较,乳腺癌组织YAP1与GR的表达水平升高。与si NC组比较,si GR组和si YAP1组的MCF-7细胞增殖能力、侵袭能力、迁移能力显著降低,凋亡率增加(P<0.05)。与si NC组比较,si GR组的MCF-7细胞的YAP1和GR表达水平降低(P<0.05),si YAP1组的MCF-7细胞的YAP1表达水平降低(P<0.05)。结论:乳腺癌患者的癌组织中YAP1与GR的表达水平升高。GR被激活后,通过调控细胞内的YAP1通路影响MCF-7细胞的增殖、迁移和侵袭能力以及凋亡率,进而导致乳腺癌MCF-7细胞转移,靶向调节YAP1抑制乳腺癌上皮间充质转化(EMT)发生可为乳腺癌患者提供新的治疗策略。

Objective:To explore the regulatory mechanism of glucocorticoid receptor(GR)and Yes-associated protein 1(YAP1)on breast cancer cell metastasis,and to provide new ideas for the treatment of breast cancer.Methods:The expression of GR and YAP1 in breast cancer tissues and adjacent tissues were analyzed by immunohistochemistry.MCF-7 cells were divided into si NC group,si GR group and si YAP1 group.The proliferation,invasion,migration and apoptosis of MCF-7 cells were analyzed by MTT assay,Transwell assay,cell scratch assay and flow cytometry,respectively.The expression levels of GR and YAP1 were analyzed by Western blotting.Results:Compared with adjacent normal tissues,the expression levels of YAP1 and GR in breast cancer tissues were increased.Compared with the si NC group,the proliferation,invasion and migration abilities of MCF-7 cells were significantly decreased in the si GR group and si YAP1 group,while the apoptosis rate was increased(P<0.05).Compared with the si NC group,the expression levels of YAP1 and GR in MCF-7 cells were decreased in si GR group(P<0.05),and the expression level of YAP1 in MCF-7 cells was decreased in si YAP1 group(P<0.05).Conclusion:The expression levels of YAP1 and GR in breast cancer tissues were increased.After the activation of GR,emotional stress hormones regulate the proliferation,migration,invasion and apoptosis of MCF-7 cells by activating the intracellular YAP1 pathway,and then lead to the metastasis of breast cancer cells.Targeted regulation of YAP1 to inhibit epithelial mesenchyme transition(EMT)of breast cancer can provide a new treatment strategy for breast cancer patients.