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表皮生长因子受体通过JAK/STAT3信号通路促进三阴性乳腺癌的发展。

EGFR Promotes the Development of Triple Negative Breast Cancer Through JAK/STAT3 Signaling.

作者信息

Song Xiang, Liu Zhaoyun, Yu Zhiyong

机构信息

Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People's Republic of China.

School of Medicine, Shandong University, Jinan, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Jan 30;12:703-717. doi: 10.2147/CMAR.S225376. eCollection 2020.

Abstract

PURPOSE

To investigate the role of EGFR and STAT3 in breast cancer development and progression.

METHODS

Through bioinformatics analysis differently expressed genes (DEGs) including EGFR and STAT3 were identified in breast cancer tissue. QRT-PCR and Western blot analysis were used to investigate EGFR and STAT3 levels in breast cancer tissues and cells. The influence of EGFR and STAT3 on the breast cancer cell proliferation (CCK-8 assay, clone formation assays), migration (wound healing assays) and invasion (transwell assays) were investigated. The influence of EGFR on breast cancer in vivo was examined by Nude mouse transplantation tumor experiments and immunohistochemistry (IHC) staining. The effects of EGFR on breast cancer signaling were assessed via Western blot.

RESULTS

Both EGFR and p-STAT3 were up-regulated in breast cancer tissues and cell lines. EGFR expression was positively associated with p-STAT3. Moreover, EGFR and p-STAT3 activity enhanced the proliferation and invasion of tumor cells. Breast cancer cell growth was dramatically inhibited by EGFR silencing in vivo.

CONCLUSION

EGFR promotes breast cancer progression via STAT3 phosphorylation and JAK/STAT3 signaling.

摘要

目的

探讨表皮生长因子受体(EGFR)和信号转导与转录激活因子3(STAT3)在乳腺癌发生发展中的作用。

方法

通过生物信息学分析,在乳腺癌组织中鉴定出包括EGFR和STAT3在内的差异表达基因(DEGs)。采用实时定量聚合酶链反应(QRT-PCR)和蛋白质免疫印迹法(Western blot)检测乳腺癌组织和细胞中EGFR和STAT3的水平。研究EGFR和STAT3对乳腺癌细胞增殖(细胞计数试剂盒-8(CCK-8)检测、克隆形成试验)、迁移(划痕愈合试验)和侵袭(Transwell试验)的影响。通过裸鼠移植瘤实验和免疫组织化学(IHC)染色检测EGFR对体内乳腺癌的影响。通过蛋白质免疫印迹法评估EGFR对乳腺癌信号传导的影响。

结果

EGFR和磷酸化STAT3(p-STAT3)在乳腺癌组织和细胞系中均上调。EGFR表达与p-STAT3呈正相关。此外,EGFR和p-STAT3活性增强了肿瘤细胞的增殖和侵袭。体内EGFR沉默显著抑制了乳腺癌细胞的生长。

结论

EGFR通过STAT3磷酸化和JAK/STAT3信号通路促进乳腺癌进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e617/6996555/de1ef877eff1/CMAR-12-703-g0001.jpg

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