igfbp4在大肠癌细胞中对wntβcatenin信号通 路调控作用的研究-regulatory effect of igf bp 4 on wnt β catenin signaling pathway in colorectal cancer cells.docx

目录中文摘要·········································································································1英文摘要·········································································································4研究论文IGFBP4在大肠癌细胞中对Wnt/β-catenin信号通路调控作用的研究前言·········································································································8材料与方法···························································································10结果·······································································································21附图·······································································································23附表·······································································································28讨论·······································································································31结论·······································································································34参考文献·······························································································35综述Wnt/β-catenin信号通路与肿瘤的研究进展···································37致谢···············································································································48个人简历·······································································································50IGFBP4在大肠癌细胞中对Wnt/β-catenin信号通路调控作用的研究摘要在世界范围内，大肠癌是危害人类健康的常见的恶性肿瘤之一，其发病率和死亡率均占第二位，并呈现逐年上升趋势。近年来，细胞内信号传导通路异常与肿瘤发生发展的关系成为医学界研究的热点问题。IGFBP4(InsulinLikeGrowthFactorBindingProtein4)，即胰岛素样生长因子结合蛋白4，是一种分泌型蛋白，其在多种正常组织中均有表达，但在大部分肿瘤中呈低表达，如肾癌、大肠癌、乳腺癌等。IGFBP4可通过调控IGFs信号系统和其它信号系统，影响细胞的增长，但后者鲜见报道。有研究发现，IGFBP4可以通过与Wnt受体Frizzled8(Frz8)竞争性结合，抑制Wnt与其受体结合活性，从而使经典Wnt/β-catenin信号通路失活；在肾癌中IGFBP4也可以通过调控经典Wnt/β-catenin信号通路而发挥作用，但在大肠癌中未见报道。目前研究已经表明Wnt/β-catenin信号通路是结直肠癌发生发展的重要机制之一，而该通路的异常激活可以介导大肠腺瘤的癌变。本课题组在前期病理组织学水平研究发现，IGFBP4蛋白表达水平在大肠正常粘膜、异型增生管状腺瘤和腺癌中依次降低，并与Wnt/β-catenin信号通路相关因子呈负相关，提示IGFBP4与Wnt/β-catenin信号通路可能存在一定的调控作用，因此