调控肿瘤细胞igf-1r信号通路的关键分子研究

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1、分类号：R73．3密级：公开单位代码：1042学号：200820791博士学位论文ShandonguniVersityoctoraloiSertation论文题目：调控肿瘤细胞IGF-1R信号通路的关键分子研究ThekeymoleculesmodulatingIGF一1RsignalingpathwayincarcinOmacellS合作导师2012年5月1O日原创性声明本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究所取得的成果。除文中已经注明引用的内容外，本论文不包含任何其他个人或集体己经发表或撰写过的科研成

2、果。对本文的研究作出重要贡献的个人和集体，均已在文中以明确方式标明。本声明的法律责任由本人承担。论文作者签名：章丝日期：硝1矿℃，“关于学位论文使用授权的声明本人同意学校保留或向国家有关部门或机构送交论文的印刷件和电子版，允许论文被查阅和借阅；本人授权山东大学可以将本学位论文的全部或部分内容编入有关数据库进行检索，可以采用影印、缩印或其他复制手段保存论文和汇编本学位论文。(保密论文在解密后应遵守此规定)论文作者签名：恤导师签名：日山东大学博士学位论文目录中文摘要···························5英文摘要···

3、························13符号说明·-·························20前言···························22刖舌·。·。·。·。·。·。·。·。ZZ第一部分G蛋白偶联受体激酶的选择性募集调控IGF一1R的信号转导及受体转运前言··························25刖百。’。‘。·。‘。·。‘。‘·。’‘。。Zb材料与方法·························26结果··························31讨论···

4、·······················38附图与附表·························42参考文献··························49第二部分IGF-lR抑制剂下调受体的分子机制研究第一节IGF-1R人源化单克隆抗体的作用及其机制研究前言·························56刖吾。’‘’。·‘。‘’‘·。·。。bb材料与方法························57结果·························59讨论··················

5、·······6l附图与附表························63第二节sunitinib泛素化下调IG卜1R的作用研究前言························-67翮舌。·’。’。’·。·’‘’。‘。‘。。b，材料与方法························68结果·························70讨论·························74参考文献·························75第三部分p53一MDM2信号通路同IGF一1R信号通路的关

6、系研究前言··························78刖吾·。·。‘。·。·‘··。，子山东大学博士学位论文第一节p53与B—arrestinl影响肿瘤细胞对IGF一1R单克隆抗体的敏感性材料与方法························79结果·························81讨论····-·················-··84第二节p53一MDM2抑制剂Nutlin_3a可降低野生型p53肿瘤细胞对紫杉醇的敏感性材料与方法························86结果··

7、·······················88讨论·························91参考文献·························93论文的主要创新点·······················97致谢··························98攻读学位期间发表的学术论文目录················99英文论文···························1002山东大学博士学位论文CONTENTSAbstrauctSiIlC11inese⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯⋯

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