干扰素诱导的跨膜蛋白IFITM3介导静息期前列腺癌细胞侵袭性转变的分子机制

项目名称： 干扰素诱导的跨膜蛋白IFITM3介导静息期前列腺癌细胞侵袭性转变的分子机制

项目编号： No.81202020

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： 洪谊

作者单位： 中国人民解放军第二军医大学

项目金额： 24万元

中文摘要： 静息期前列腺癌是组织学上为恶性肿瘤但不具有侵袭生长生物行为的病理现象，其向侵袭性前列腺癌转变的分子机制还不甚清晰。本课题组在前期工作中通过基因芯片筛选和免疫组化证实干扰素诱导跨膜蛋白IFITM3在侵袭性前列腺癌发灶中高表达而在静息期前列腺癌中表达甚低或不表达，提示IFITM3可能参与调控前列腺癌细胞由静息期向侵袭性的恶性转变。细胞实验证实这种作用与其在前列腺癌细胞中介导增殖和转移的生物学功能密切相关，且IFITM3介导转移功能与前列腺癌细胞的上皮-间质转化（EMT）存在联系。本课题拟在此基础上，在体内、外实验中进一步探讨IFITM3及其下游信号分子通路对前列腺癌细胞侵袭转移发生的影响与分子机制；通过裸鼠转移瘤模型研究下调IFITM3对前列腺癌细胞侵袭、转移能力的影响；同时，利用100例前列腺癌病人组织样本验证IFITM3在前列腺癌中的表达水平与肿瘤恶性程度、转移现象以及预后之间的关联性。

中文关键词： IFITM3；前列腺癌；骨转移；；

英文摘要： Quiescent prostate cancer is the malignant tumor from the pathological view, which does not invade into adjacent tissue or metastasis to remote position. The transformation mechanism of quiescent prostate cancer to the invasive state has not been well studied. In order to clarify the mechanism, the applicant performed a genechip analysis of gene expression profiles in the quiescent prostate cancer samples and primary and metastatic samples from the invasive prostate cancer. The result shows that interferon induced transmembrane protein 3 (IFITM3) is elevated in the invasive prostate cancer and especially in the bone metastatic samples, indicating that IFITM3 may play a pivotal role in regulating the transformation of prostate cancer from quiescent to invasive status. Cell based studies indicates that knockdown of IFITM3 expression inhibits the proliferation, migration, and invasion of prostate cancer cells. Molecualar analysis proves that down regulation of IFITM3 expression reduces the expression of E-cadherin whereas upregulates fibronectin level, suggesting a connection of IFITM3 to EMT process. Based on these preliminary results, this proposal designs in vitro and in vivo experiments to uncover the mechnisms and downstream molecular network of IFITM3 mediated invasive transformation of prostate cancer. Meanw

英文关键词： IFITM3；Prostate cancer；Bone metastasis；；