ERβ2/p38MAPK信号通路轴通过上调IL-12Rβ2表达抑制NSCLC进展机制的研究

项目名称： ERβ2/p38MAPK信号通路轴通过上调IL-12Rβ2表达抑制NSCLC进展机制的研究

项目编号： No.81501964

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘昭国

作者单位： 中山大学

项目金额： 18万元

中文摘要： 研究发现：雌激素受体β（ERβ）及IL-12Rβ2可能发挥抑制非小细胞肺癌（NSCLC）进展的作用，但其具体机制不明确。前期研究显示：在NSCLC中，ERβ2是ERβ主要表达亚型，高表达ERβ2与IL-12Rβ2具有良好预后作用， IL-12Rβ2表达受ERβ2/p38MAPK调控，且ERβ2功能依赖于IL-12Rβ2。我们推测：ERβ2/p38MAPK信号通路轴可能通过上调IL-12Rβ2表达进而发挥抑制NSCLC进展的作用。本项目拟分析ERβ2、IL-12Rβ2与血清雌二醇（E2)关系，并验证其预后作用；通过蛋白质表达干预、启动子活性检测等手段，验证ERβ2/p38MAPK上调IL-12Rβ2表达；通过细胞及动物实验，探讨ERβ2/p38MAPK/IL-12Rβ2抑制NSCLC进展的机制。本项目的完成将证实前期研究，为确立ERβ2及IL-12Rβ2作为防治NSCLC新靶点提供科学依据。

中文关键词： 非小细胞肺癌；雌激素受体β2；白介素12受体β2；丝裂素活化蛋白激酶p38

英文摘要： Some researches reported that estrogen receptor beta (ERβ) and interleukin-12 receptor beta 2(IL-12Rβ2) may inhibit non- small cell lung cancer(NSCLC) development, and are good independent prognostic factors, but the mechanisms on this roles in NSCLC is unclear. In our previous studies, we showed that estrogen receptor beta2 (ERβ2) may coexpress with interleukin-12 receptor beta 2(IL-12Rβ2), there are significant association between them, and ERβ2 and IL-12Rβ2 are good prognostic factors in NSCLC. Moreover, we showed that there are interaction between p38MAPK and IL-12Rβ2, IL-12Rβ2 expression can be upregulate by ERβ2/p38MAPK signaling pathway..To sum, we hypothesize that ERβ2/p38MAPK may inhibit NSCLC development via upregulating IL-12Rβ2 expression. In this research, we will detect expression of ERβ2, p38MAPK and IL-12Rβ2 in clinic tissues, analysis the relation between them, serum estradiol (E2) level and pathological features and endeavor to clarify these mechanisms that ERβ2 regulate IL-12Rβ2 expression and IL-12Rβ2 gene promoter activity via Co-immunoprecipitation(CoIP), intervening protein expression (e.g., constructing cell plasmids ) and detecting promoter activity(e.g., Dual luciferase reporter gene technology. At the same time, in our previous study basis, we will explore further how high expression of ERβ2 inhibit NSCLC progress via IL-12Rβ2 by some cell technology and lung transplantation tumor model. The completion of the project will further validate our preliminary studies, and reveal partial mechanisms on ERβ2 regulating NSCLC development，and support the reliable theoretical basis for new NSCLC treatment.

英文关键词： NSCLC;ERβ2;IL-12Rβ2;p38MAPK