跨膜蛋白MS4A8B在前列腺癌癌变过程中的功能及分子机制

项目名称： 跨膜蛋白MS4A8B在前列腺癌癌变过程中的功能及分子机制

项目编号： No.81472389

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 姚旭东

作者单位： 同济大学

项目金额： 72万元

中文摘要： 前列腺癌生物学行为复杂，四跨膜结构域A亚家族(MS4A)在肿瘤病理过程中的作用研究不多。MS4A8B是我们使用软件对前列腺癌高通量数据筛选到的一个MS4A蛋白。我们前期工作显示，MS4A8B在前列腺癌组织中特异高表达并与术后生化复发相关，体内外实验可促进前列腺癌细胞增殖，然而其作用机制及意义有待研究。通过结构分析及预实验，我们发现MS4A8B基因表达可能受雄激素受体(AR)转录调控，同时下调MS4A8B导致pAKT表达降低。因此，本项目提出MS4A8B通过雄激素反应构件(ARE)与AR结合而转录增加，作为衔接蛋白通过一系列信号转导机制最终通过AKT通路实现细胞增殖的假说。为此，我们将采用双荧光素酶报告基因、Co-IP、ChIP等手段，从分子、细胞、组织和动物水平探讨MS4A8B在前列腺癌进展过程中的作用机制。本项目将从MS4A蛋白角度揭示前列腺癌病理过程的新机制，为前列腺癌治疗提供新靶点。

中文关键词： C14_前列腺肿瘤；四跨膜结构蛋白A亚家族成员8B；雄激素受体；增殖

英文摘要： The biological behaviors of prostate cancer are a complex. The study of MS4A is rare in pathological process of tumor. We used bioinformatics software to analyze high-throughput data of prostate cancer and identified a MS4A protein, MS4A8B. Our preliminary work results revealed that MS4A8B over-expresses specifically in prostate cancer and correlate with biochemical recurrence after radical prostatectomy, and promotes prostate cancer cells proliferation in vitro and in vivo, but the mechanism underlying was unknown. By our structure analysis and pre-experiments, we found MS4A8B expression might be regulated transcriptionally by androgen receptor, meanwhile, down-expression of MS4A8B resulted in low expression of p-AKT. Therefore, we put forward the hypothesis that MS4A8B over-expressed transcriptionally by its ARE binding with AR, and promotes cell proliferation by AKT pathway at last as a adaptor protein. For this purpose, we will use dual-luciferase report, Co-Immunoprecipitation and ChIP technology and so on to explore the molecular mechanism of MS4A8B in the initiation and progression of prostate cancer, by molecular, tissues, in vitro and in vivo. This study will originally reveal a new mechanism of prostate cancer from MS4A8B angle, and provide new therapeutic targets for prostate cancer.

英文关键词： Prostate Cancer;MS4A8B;Androgen Receptor;Proliferation