ERK/MAPK信号通路活性表达与鼻咽癌细胞增殖凋亡的关系  

Relationship between activation of ERK/MAPK signal way and proliferation and apoptosis in nasopharyngeal carcinoma cells

作　　者：黄坊[1] 谢明[2] 景志亮[1] 赵颖海[1] 

机构地区：[1]广东医学院病理学教研室,广东湛江524023 [2]中国人民解放军第四二二医院病理科,广东湛江524005

出　　处：《中华肿瘤防治杂志》2010年第15期1192-1195,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：湛江市科技公关计划项目

摘　　要：目的:探讨鼻咽癌细胞中ERK/MAPK信号传导通路异常激活与细胞增殖凋亡的关系。方法:SP法检测36例鼻咽癌、42例对照鼻咽黏膜上皮中p-ERK、CyclinD1和Ki-67蛋白的表达。用不同浓度阻滞剂PD98059处理CNE-2Z细胞,Hoechst33342/PI荧光双染法观察细胞凋亡,流式细胞仪检测凋亡,蛋白质印迹法检测CyclinD1蛋白表达,免疫细胞化学法检测p-ERK、CyclinD1和Ki-67蛋白的表达。结果:鼻咽癌组织中p-ERK、CyclinD1和Ki-67的阳性表达率分别为69.44%(25/36)、80.56%(29/36)和80.56%(29/36),鼻咽黏膜上皮组织中则分别为23.80%(10/42)、19.05%(8/42)和9.52%(4/42),P<0.01。鼻咽癌组织中p-ERK与CyclinD1、Ki-67蛋白的表达呈正相关,r分别为0.604和0.668,P均<0.01。不同浓度PD98059作用于CNE-2Z细胞后,可观察到凋亡细胞,检测到凋亡峰,CyclinD1蛋白表达的减少呈剂量依赖性,p-ERK、CyclinD1和Ki-67蛋白的阳性表达细胞数减少。结论:鼻咽癌组织及CNE-2Z细胞中存在p-ERK蛋白的高表达和活化异常,p-ERK可能通过上调CyclinD1和Ki-67的表达促进鼻咽癌细胞增殖并抑制凋亡。ERK信号通路有可能成为鼻咽癌治疗的新靶点。OBJECTIVE：To study the effect of treatment with ERK/MAPK signal way inhibitors PD98059 on proliferation and apoptosis in the human nasopharyngeal cancer cells,and evaluate the relationship between them.METHODS：The SP method was adopted to detect the expressions of p-ERK,Cyclin D1 and Ki-67 proteins in 36 cases of NPC and 42 cases of nasopharyngeal mucosal epithelium and CNE-2Z cells.CNE-2Z cells were treated with different doses of PD98059.Hoechst33342/Propidium iodide double-staining and flow cytometry were used to observe the apoptosis in CNE-2Z cells.Western-blot was adopted to detect the expression of Cyclin D1 protein in CNE-2Z cells.RESULTS：The positive staining rates of p-ERK,Cyclin D1 and Ki-67 proteins in NPC were 69.44%（25/36）,80.56%（29/36） and 80.56%（29/36） respectively.The positive staining rates of the proteins in nasopharyngeal mucosal epithelium were 23.80%（10/42）,19.05%（8/42） and 9.52%（4/42） respectively （P〈0.01）.There were statistically significant positive correlations between the positive p-ERK expression and positive expressions of Cyclin D1 and Ki-67（r were 0.604 and 0.668,and P〈0.01）.When CNE-2Z cells treated by the different doses of PD98059,the apoptosis was observed,the expressions of p-ERK,Cyclin D1 and Ki-67 proteins were decreased detected,and Cyclin D1 protein was downregulated detected.CONCLUSIONS：Abnormally over expression and activating of p-ERK protein exists in NPC tissues and CNE-2Z cells.P-ERK promotes NPC cells proliferation and inhibits the apoptosis through up-regulating the expressions of Cyclin D1 and Ki-67 proteins.ERK signal way may be a new therapeutic target in nasopharyngeal cancer.

关 键 词：鼻咽肿瘤 细胞外信号调节激酶 增殖 

分 类 号：R739.63[医药卫生—肿瘤]