项目名称: SOX2蛋白的磷酸化分析及其在胶质母细胞瘤中的作用和分子机制研究
项目编号: No.81201640
项目类型: 青年科学基金项目
立项/批准年度: 2013
项目学科: 肿瘤学1
项目作者: 沈虹
作者单位: 浙江大学
项目金额: 23万元
中文摘要: 胶质母细胞瘤 (GBM)是一种常见的和恶性程度最高的颅内原发肿瘤,其患者预后差。目前对GBM的发病机制了解甚少。我们前期工作发现SOX2在GBM中扮演癌基因角色,在转录调控水平探讨了其致瘤作用的分子机理,并发现SOX2蛋白为磷酸化蛋白,本项目拟在以往研究工作基础上在翻译后水平探讨SOX2蛋白的磷酸化在GBM中的作用和分子机制,在细胞系和动物模型中研究SOX2蛋白的磷酸化对细胞增值和迁移能力的影响;分析磷酸化对SOX2蛋白对靶基因转录调控能力以及自身稳定性的影响;应用IP、GST-pulldown和基因转染探讨SOX2与AKT直接相互作用而调控SOX2磷酸化;MRM定量蛋白质组学技术分析SOX2蛋白的磷酸化与肿瘤分期以及转移之间的关系,本研究对深入理解SOX2在GBM中作用的分子机理以及寻找新的治疗靶点具有重要现实意义。
中文关键词: 胶质母细胞瘤;SOX2;磷酸化;AKT;
英文摘要: Glioblastoma multiforme (GBM) is a common and the most malignant primary intracranial tumors, the patients'prognosis is very poor. So far, its pathogenesis is poorly understood. Our previous work found that SOX2 plays oncogene role in GBM and we did some research about its molecular mechanism at the level of transcriptional regulation. We also found that SOX2 protein was phosphorylated proteins. The purpose of our research project is to investigate the role of SOX2 protein phosphorylation in GBM and its molecular mechanism, SOX2 protein phosphorylation sites Mass spectrometry in the GBM cells; SOX2 protein phosphorylation on cell proliferation and migration in cell lines and animal models; phosphorylation of SOX2 protein on gene expression regulation of target gene and its stability in cells; IP、GST-pulldown and gene transfection are applied to analyze interaction of SOX2 and AKT protein and SOX2 phosphorylated by AKT. The relation of SOX2 phosphorylation and cancer metastasis is analyzed by MRM absolute quantification method. Our study is important for further understanding of the molecular mechanism of SOX2 in the GBM role and to find new therapeutic targets.
英文关键词: GBM;SOX2;phosphorylation;AKT;