蛋白激酶CK2促进脑肿瘤起始细胞存活的机制研究  

Mechanism of Protein Kinase CK2 Promoting the Survival of Brain Tumor-initiating Cells

作　　者：吴海涛 陈小忠 赵洪新 申昊 杨朝志 岳翔 张平 王培 Wu Haitao;Chen Xiaozhong;Zhao Hongxin;Shen Hao;Yang Chaozhi;Yue Xiao;Zhang Pin;Wang Pei(The Affiliated Hospital of Zunyi Medical University,Zunyi,563000)

机构地区：[1]遵义医科大学附属医院

出　　处：《基因组学与应用生物学》2019年第10期4750-4756,共7页Genomics and Applied Biology

基　　金：2019年遵义市联合基金项目(遵市科合HZ字(2019)79号)资助

摘　　要：蛋白激酶CK2是一种表达丝氨酸/苏氨酸的激酶,由两个催化亚基(α或α')和两个调节亚基(β)组成的不均一四聚体。在许多不同的癌症中,均发现蛋白激酶CK2的表达和活性升高,包括胶质母细胞瘤(GBM)。本研究使用细胞培养并分离小鼠脑组织,形成神经球,使用流式细胞仪,免疫印迹和细胞实验对脑肿瘤起始细胞(BTIC)的存活机制进行研究。结果显示,与相同GBM异种蛋白内的CD133-细胞相比,CD133+BTIC中蛋白激酶CK2α亚基的表达量增加。利用ATP竞争性蛋白激酶CK2抑制剂CX-4945治疗,导致Sox2和Nestin的表达降低,其中Sox2和Nestin是对维持干细胞很重要的转录因子。本实验的研究结论初步表明,由于蛋白激酶CK2在对BTIC存活重要的多种信号传导途径中起关键作用,蛋白激酶CK2是GBM中有希望的靶标。Protein kinase CK2 is a serine/threonine-expressing kinase consisting of two heterogeneous tetramers consisting of two catalytic subunits(αorα')and two regulatory subunits(β).Increased expression and activity of protein kinase CK2,including glioblastoma(GBM),has been found in many different cancers.In this research mouse brain tissue was isolated and cultured to form neurospheres,the survival mechanism of brain tumor initiation cells(BTIC)was investigated by flow cytometry,immunoblotting and cell experiments.The expression of the protein kinase CK2αsubunit in CD133+BTIC was increased compared to CD133-cells in the same GBM heterologous protein.Treatment with the ATP-competitive protein kinase CK2 inhibitor CX-4945 resulted in decreased expression of Sox2 and Nestin,a transcription factor important for maintaining stem cells.Our research conclusions preliminarily indicated that protein kinase CK2 should be a promising target in GBM,as protein kinase CK2 plays a key role in multiple signaling pathways important for BTIC survival.

关 键 词：胶质母细胞瘤 蛋白激酶CK2 脑肿瘤起始细胞(BTIC) EGFR 

分 类 号：R73[医药卫生—肿瘤]