| 摘要 | 第1-12页 |
| Abstract | 第12-13页 |
| Abbreviation | 第13-14页 |
| Chapter Ⅰ:Introducton | 第14-36页 |
| ·The Bcr-Ab1 tyrosine kinase and generation of chronic myeloid leukemia(CML) | 第14-17页 |
| ·The roles of Ab1 interactor(Abi) in cells | 第17-36页 |
| ·The discovery of Abi family proteins | 第17-20页 |
| ·Abi interacts with Ab1 and influence the signal transduction regulated by Ab1 tyrosine kinase | 第20-24页 |
| ·Abi could form Eps8-Abi1-Sos1 complex involved in Eps8 pathway | 第24-27页 |
| ·The function of Abi family in actin polymerization through interacting with WAVE/WASP family members | 第27-36页 |
| Chapter Ⅱ:Investigation of the role of Abi2 protein in tumor cells | 第36-66页 |
| ·Material and methods | 第36-42页 |
| ·Cell culture and reagent | 第36-37页 |
| ·In vitro translation assay | 第37-38页 |
| ·Cell cycle synchronization | 第38-39页 |
| ·SDS-PAGE and western blotting | 第39页 |
| ·Immunoprecipitation | 第39-40页 |
| ·In vitro phosphorylation Kinase assays | 第40页 |
| ·Plasmid constructs | 第40-41页 |
| ·Fluorescence microscopy | 第41-42页 |
| ·Results | 第42-63页 |
| ·Dysregulation of Abi1 and Abi2 by Bcr-Ab1 in BaF3p185wt cells | 第42-44页 |
| ·Define the sequences in Abi2 that are required for Bcr-Ab1-induced downregulation | 第44-50页 |
| ·Identification of molecular events downstream of Bcr-Ab1/Abi1 signaling | 第50-53页 |
| ·Deferential regulation and function of Abi1 and abi2 isoforms in vivo | 第53-58页 |
| ·Abi2B/A is involved in the regulation of MMP-9 expression in MDA-MB231 cells | 第58-60页 |
| ·Abi is phosphorylated by CDC2 in a cell-cycle dependent fashion | 第60-63页 |
| ·Discussion | 第63-66页 |
| Chapter Ⅲ:Abi1 regulates MMP9 expression and invadopodia formation | 第66-93页 |
| ·Material and methods | 第67-75页 |
| ·Cells cultures | 第68-69页 |
| ·Transfection | 第69-70页 |
| ·Antibodies and reagents | 第70页 |
| ·Immunocytochemistry and fluorescence microscopy | 第70-71页 |
| ·In vitro ECM degradation assay | 第71-72页 |
| ·Cell migration and proliferation assays | 第72页 |
| ·Biochemical assays | 第72-73页 |
| ·Real-time quantitative reverse transcription-PCR | 第73-74页 |
| ·In vivo tumorgenesis studies | 第74-75页 |
| ·Statistical analyses | 第75页 |
| ·Results | 第75-89页 |
| ·Abi1 is found in invadopodia in MDA-MB231 cells | 第75-79页 |
| ·Abi1 silencing inhibited invadopodia formation and ECM degradation of MDA-MB231 cells | 第79-81页 |
| ·Abi1 is involved in the regulation of MMP-9 expression in MDA-MB231 cells | 第81-84页 |
| ·Activation of Src tyrosine kinase is essential for the regulation of Id1/MMP-9 expression and formation of invadoodia in MDA-MB231 cells | 第84-86页 |
| ·Abi1 silencing inhibited the Src-Id1 signaling and impaired MDA-MB231 cell migration and proliferation | 第86-88页 |
| ·Knockdown of Abi1 expression markedly slowed tumor growth of MDA-MB231 breast cancer cells | 第88-89页 |
| ·A hypothetical model of the Abi1 signaling that regulates invadopodia formation and the Src pathway in MDA-MB231 breast cancer cells | 第89页 |
| ·Discussion | 第89-93页 |
| Conclusions | 第93-96页 |
| References | 第96-115页 |
| 攻读博士期间发表的学术论文 | 第115-116页 |
| 致谢 | 第116-118页 |
| 学位论文评阅及答辩情况表 | 第118页 |
