胶质瘤表达抗原2（GLEA2)通过ROS-JNK通路对神经胶质瘤杀伤作用的机制研究

项目名称： 胶质瘤表达抗原2（GLEA2)通过ROS-JNK通路对神经胶质瘤杀伤作用的机制研究

项目编号： No.81201985

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： 李玉文

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 神经胶质瘤作为常见的颅内肿瘤，是全身预后最差的肿瘤之一。胶质瘤表达抗原GLEA2(Glioma-Expressed Antigen)是新发现的胶质瘤表达抗原，多项临床研究指出其和患者的预后息息相关。但是GLEA2在肿瘤中的生物学特性及调节机制在国际上尚未有文章报道。我们前期研究发现，GLEA2杀伤神经胶质瘤细胞，而且过表达GLEA2诱导细胞内活性氧(ROS)含量明显增多，进而激活了调节细胞死亡的关键性蛋白：JNK。提示GLEA2在胶质瘤发展中的负性调节作用。基于这一发现，本研究将利用基因转染，基因沉默技术，流式细胞术，免疫组化，免疫电镜技术，裸鼠肿瘤移植模型等方法深入探讨GLEA2对神经胶质瘤细胞的杀伤作用，通过多重免疫荧光，免疫印迹等方法研究GLEA2诱导ROS增高激活JNK杀伤肿瘤细胞的的分子机制。完成本课题对揭示胶质瘤发生发展，确立新的胶质瘤基因治疗靶点及患者的预后判断具有重要意义。

中文关键词： 胶质瘤表达抗原；胶质瘤；活性氧；c-Jun氨基末端激酶；坏死性细胞死亡

英文摘要： As a common intracalvarium tumor, glioma is one of the worst prognostic tumors. Glioma expressed antigen 2（GLEA2） is a novel identified glioma antigen, GLEA2 was implied significantly correlated with prolonged survival in clinic studies. However, biological character and regulatory mechanism of GLEA2 in tumors are still not reported yet. Our premilinary study showed overexpression of GLEA2 in U251 glioma cells induced cell death. Moreover, reative oxidative species (ROS) was significantly increased in GLEA2-overexpressed U251 cells, subsquently, a key regulator in cell death pathway: c-Jun N-terminal kinase (JNK) was activated. Taken together, GLEA2 could be considered a regulator of glioma cell fate and a putative powerful tool against glioma growth. In light of our findings, we sight to investigate key role of GLEA2 in glioma development by generating glioma transplanted nude mice, and using various molecular techniques, such as tranfection, siRNA, fluorescence activated cell sorting (FACS) and immunohistochemistry. Furthermore, we will reveal molecular regulatory mechanism of GLEA2 mediated ROS generation and JNK activation by using multiple immunofluorescence,confocal microscope,western-blotting and so on. Finally, we will indicate contribution of ROS-JNK pathway to GLEA2 induced cell death. The study will o

英文关键词： GLEA2；Glioblastoma；ROS；JNK；Necrotic cell death