ATM在人胃癌细胞系的表达及其在细胞DNA损伤中的作用  

Expression of ATM gene in human gastric carcinoma cell lines and cellular responses to DNA damage

作　　者：王莉[1] 尹芳[1] 杜昱蕾[1] 杜文琪[1] 陈蓓[1] 张永国[1] 陈铮[1] 乔泰东[1] 樊代明[1] 

机构地区：[1]第四军医大学西京医院消化病院肿瘤生物国家重点实验室,陕西西安710032

出　　处：《现代肿瘤医学》2010年第3期433-436,共4页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:C03031905)

摘　　要：目的:研究DNA损伤剂对ATM基因缺陷和正常的胃癌细胞系的作用机制。方法:Western-blot方法检测6株胃癌细胞系ATM蛋白的表达情况,并用DNA损伤剂顺铂作用于ATM基因缺陷的MKN28细胞系和ATM基因正常的BGC823细胞系,采用Western-blot、DNAladder、Hoechest33258/PI双荧光染色等方法观察凋亡相关激酶的表达和细胞的应答反应。结果:Western-blot显示,ATM蛋白在胃癌细胞系MGC803、MKN28、MKN45、SGC7901的表达水平显著低于BGC823和AGS细胞系,BGC823细胞在CDDP作用后,ATM蛋白表达水平升高,磷酸化chk1和chk2活性24小时后增强,而Cdc25C表达减少;MKN28细胞中G2期检测点蛋白ATM、p-chk1、p-chk2表达较低,Cdc25C表达较高,但在CDDP作用前后无明显变化。MKN28细胞在DNA损伤剂作用后出现显著凋亡,而BGC823细胞在DNA损伤剂作用48小时后未见显著凋亡。结论:ATM在细胞周期的多个环节均有调控作用,特别是在细胞周期检测点和DNA损伤的修复中有重要的监视和启动作用。Objective：To investigate the expression of ATM gene in six human gastric cancer cell lines and cellular responses to DNA damage. Methods： Western - blot analysis was performed on six human gastric cancer cell lines, and the apoptosis kinases and cellular responses were observed after two cell lines MKN28 and MGC803 were treated with the DNA damage reagent CDDP. Results ： It was found that ATM was strongly expressed in MGC803, MKNg8, MKN45, SGC7901 cell lines ,but it weekly expressed in BGC823 and AGS cell lines. The level of ATM pro- tein and apoptosis kinases in BGC823 were increased after treated with CDDP, while the G2 phase checkpoint of MKN28 cells was deficient because the expressions of ATM ,p - chkl and p - chk2 were weak after treated with CD- DP （P 〈 0.05 ）. Conclusion： ATM deficiency may lead to apoptosis and sensitiveness to DNA damage. ATM may control multiple component elements in cell cycle and monitor cell cycle check point to restoration of cells after DNA damage.

关 键 词：ATM 胃癌 DNA损伤 凋亡 DNA LADDER Western—blot 

分 类 号：R730[医药卫生—肿瘤] R735.2[医药卫生—临床医学]