17β-estradiol upregulates IL6 expression through the ERβ pathway to promote lung adenocarcinoma progression

作者：Quanfu Huang, Zheng Zhang, Yongde Liao, Changyu Liu, Frank S. Fan, Wei Xiao, Bo Ai, Jing Xiong · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2018 · DOI：10.1186/s13046-018-0804-5 · 被引用次数：63 · 研究领域：Estrogen and related hormone effects、Protein Kinase Regulation and GTPase Signaling、Cytokine Signaling Pathways and Interactions

BACKGROUND: In non-small cell lung cancer (NSCLC), estrogen (E2) significantly promotes NSCLC cell growth via estrogen receptor beta (ERβ). Discovery and elucidation of the mechanism underlying estrogen-promoted NSCLC progression is critical for effective preventive interventions. IL6 has been demonstrated to be involved in the development, progression and metastasis in several cancers and IL6 overexpression is associated with poor prognosis in NSCLC. However, the exact role played by IL6 in estrogen-promoted NSCLC progress remain unknown. Here, we evaluated the expression and biological effects of IL6 in NSCLC cells when treated with E2 and explored the underlying mechanism of IL6 in E2-promoted NSCLC progression. METHODS: Expression of ERβ/IL6 in 289 lung cancer samples was assessed by immunohistochemistry. Matched samples of metastatic lymph node and primary tumor tissues were used to quantify the expression of ERβ/IL6 by western blot. Expression levels of IL6 in NSCLC cells were quantified by western blotting, ELISA, and immunofluorescence staining. The effects of IL6 stimulated by E2 on cell malignancy were evaluated using CCK8, colony formation, wound healing and transwell. Furthermore, overexpression and knockdown ERβ constructs were constructed to measure the expression of IL6. The effects of IL6 stimulated by E2 on tumor growth were evaluated using a urethane-induced adenocarcinoma model. In addition, a xenograft mouse model was used to observe differences in ERβ sub...