条件性剔除JWA基因引起微环境改变对肿瘤生长和转移的影响和机制

项目名称： 条件性剔除JWA基因引起微环境改变对肿瘤生长和转移的影响和机制

项目编号： No.91229125

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 周建伟

作者单位： 南京医科大学

项目金额： 110万元

中文摘要： 恶性肿瘤是严重威胁人类健康的重要疾病，也是目前值得关注和亟待解决的公共卫生问题。阐明肿瘤微环境对肿瘤发生发展的影响和调节规律，是当前肿瘤研究的前沿和热点，对于制定科学的肿瘤防治策略，最终实现个体化治疗具有非常重要的意义。本项目在申请人对新的肿瘤抑制基因JWA研究15年取得重要新发现基础上，针对JWA通过NFkB和E2Fs调节体内微环境影响肿瘤生长和转移的关键环节，以剔除JWA引起的免疫和炎症分子网络紊乱为主线，利用原创性的JWA基因剔除小鼠以及进一步拓展的JWA/Rela双基因剔除以及E2Fs转基因等策略，逆转对小鼠荷瘤和转移瘤的转归；结合对高通量数据的生物信息学分析和建立模型等，最终提出剔除JWA促进肿瘤生长和转移的免疫、炎症微环境中细胞和分子网络特征，为从干预微环境角度提出防治肿瘤新思路提供依据。

中文关键词： JWA基因；微环境；黑色素瘤转移；结肠炎-癌转化；信号通路

英文摘要： Both the morbidity and mortality of cancer is still a big challenge to human beings worldwide although the scientists paid more and more attention and efforts to cancer research during past decades. In normal tissues and organs, the activities of the constituent cells are strictly restricted to the tasks assigned to them during development. In contrast, the microenvironment in regions where tumors are forming and expanding is characterized by progressive loss of specialized or differentiated cellular functions, disorderly molecular signals, degeneration of microscopical organ structure. Our recent novel findings indicated that JWA knockout mice formed microenvironment promoting tumor growth and metastasis, and might be linked to disordered molecular signals by abnormal activation of NFkappaB signal pathway; at the same time inhibition of E2Fs signals. To elucidate JWA knockout produced characteristics of microenvironment and the potential molecular mechanisms on tumor growth and metastasis, we are going to use multiple modern research techniques, including conditional double knockout JWA and rela and target gene(s) transgenic strategy, systematic analysis of this disorder of micorenvironment in JWA knockout mice, especially focus on the global changes of immune and inflammation molecules in the microenvironment

英文关键词： JWA；microenvironment；melanoma metastasis；colitis-colon cancer；signal pathways