分化/DNA结合抑制因子-1在肌层浸润性膀胱癌发生和进展中的作用及机制研究

项目名称： 分化/DNA结合抑制因子-1在肌层浸润性膀胱癌发生和进展中的作用及机制研究

项目编号： No.81201996

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： 胡浩

作者单位： 北京大学

项目金额： 23万元

中文摘要： 目前，肌层浸润性膀胱癌发生和进展的分子生物学机制还没有明确。研究证明，分化/DNA结合抑制因子-1（inhibitor of differentiation/DNA binding-1，Id-1）作为一种致癌基因与多种恶性肿瘤的进展和耐药相关。我们的前期体外实验证明，Id-1表达与膀胱癌上皮向间质转化有关，提示其与膀胱癌进展的相关性；而且Id-1上调能够降低膀胱癌细胞系对药物化疗的敏感性。本研究将进一步利用膀胱癌患者组织标本及随访资料，研究Id-1与肌层浸润性膀胱癌的进展及预后的相关性；通过利用Id-1上调和下调的膀胱癌细胞模型，筛选Id-1在膀胱癌进展过程中可能的相互作用分子及信号通路；还将通过膀胱癌原位生物发光小鼠模型，体内实验证实Id-1表达对肌层浸润性膀胱癌发生和进展的影响和分子机制，以及对药物化疗敏感性的影响。可望通过本研究阐明Id-1在肌层浸润性膀胱癌发生和进展中的作用和机制。

中文关键词： 分化/DNA结合抑制因子-；膀胱癌；干细胞；；

英文摘要： The molecular mechanism of tumorigenesis and progression in muscle invasive bladder caner is still unclear. It has been shown that inhibitor of differention/DNA binding-1(Id-1) is a potential oncogene which is related with tumor progression and drug resistance. Our preliminary study has shown that activation of Id-1 can lead to the induction of epithelial to mesenchymal transition（EMT）, which contributes to tumor progression, including invasion and metastasis. Moreover, up-regulation of Id-1 in bladder cancer cells leads to increased cell viability in response to epirubicin by its improved anti-apoptotic role, and down-regulation of Id-1 increases cellular sensitivity to epirubicin by increased anticancer drug-induced apoptosis. In this project, we will make use of pathological tissue samples and follow-up data to investigate the correlation between Id-1 and the progression or prognosis for muscle invasive bladder cancer patients. We will also screen the possible interactive molecules and signaling pathways by the bladder cancer cell line models with Id-1 up-regulation or down-regulation. In addition, the bladder tumor in situ bioluminescent mouse model will be used to study the effects of Id-1 on the initiation and progression in muscle invasive bladder cancer, and to verify the interactive molecules and signal

英文关键词： Id1；bladder cancer；stem cell；；