GRP78在结直肠癌中表达改变机制的研究

项目名称： GRP78在结直肠癌中表达改变机制的研究

项目编号： No.81201947

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2

项目作者： 邢晓明

作者单位： 青岛大学

项目金额： 23万元

中文摘要： 本研究在蛋白质组学研究的基础上，对差异筛选到得一个在结直肠癌中高表达的蛋白质GRP78（糖调节蛋白78）进行了进一步的分析。利用RNA干扰技术抑制GRP78在结直肠癌细胞系RKO中的表达，研究该蛋白表达变化对RKO细胞生长，增殖、凋亡、细胞周期等生物学行为、抗应激能力及对化疗药物敏感性的影响，并通过体内实验观察其表达变化对肿瘤生成的影响；同时利用免疫共沉淀结合质谱分析的方法，从整体水平上明确与GRP78表达相关的信号转导通路中各蛋白的变化。最终阐明GRP78在结直肠癌发生、发展中的作用，为GRP78作为临床基因治疗新靶点提供理论依据。

中文关键词： 结直肠癌；GRP78；增殖；基因芯片；凋亡

英文摘要： .Glucose regulated protein 78 (GRP78), which was isolated by differential proteomic screening and highly expressed in colorectal carcinoma, will be further investigated in the current study. Using RNA interference, GRP78 expression in colorectal cancer cell line RKO was downregulated. Based on the these previously completed work, the influence of GRP78 differential expression on biological behalviors (including growth, proliferation, apoptosis and cell cycle), anti-stress capability and sensitivity to chemotherapy agents of RKO cell will be investigated. In vivo study will also be performed to study the influence of GRP78 differential expression on tumorigenesis. In addition, co-immunoprecipitation and mass spectrometry will be applied to determine changes of proteins in signal transduction pathways related to GRP78 expression. The effects of GRP78 on the occurence and progression of colorectal cancer will be elucidated eventually and these will provide theoretical evidence for using GRP78 as a novel gene therapeutic target in the clinical treatment of colorectal cancer.

英文关键词： colorectal carcinoma；GRP78；proliferation；genechip；apoptosis