哈萨克族食管癌患者组织中细胞外信号调节激酶／丝裂原活化蛋白激酶信号通路的表达  

Expression of ERK1/2 MAPK signaling transduction pathway in esophageal cancers in Kazakh patients

作　　者：郑树涛[1] 刘涛[1] 阿孜古丽·吐尔逊[1] 霍奇[1] 刘清[1] 黄丛改[1] 冯军国[1] 吕国栋[1] 王星[1] 林仁勇[1] 伊力亚尔·夏合丁 卢晓梅[1] 

机构地区：[1]新疆医科大学第一附属医院医学研究中心,乌鲁木齐830054 [2]新疆维吾尔自治区食管癌研究所

出　　处：《中华肿瘤杂志》2011年第6期421-425,共5页Chinese Journal of Oncology

基　　金：国家自然科学基金（30760223、30860097）

摘　　要：目的探讨细胞外信号调节激酶（ERK）／丝裂原活化蛋白激酶（MAPK）信号通路在哈萨克族食管鳞癌患者组织中的表达变化及意义。方法采用Western blot技术检测在血清饥饿条件下、U0126梯度浓度处理下，食管癌细胞系EC9706中磷酸化ERK1（p-ERK1）和磷酸化ERK2（p-ERK2）的表达变化。采用实时荧光定量PCR法检测25例哈萨克族食管癌患者肿瘤组织和癌旁正常组织中总ERK1（t-ERK1）和总ERK2（t-ERK2）mRNA的表达变化。采用Western blot技术检测25例哈萨克族食管癌患者肿瘤组织、癌旁正常组织以及5例哈萨克族非食管癌者正常食管组织中t-ERK1、t-ERK2、p-ERK1和p-ERK2蛋白的表达变化。采用免疫组化染色法，在126例石蜡包埋标本（正常食管黏膜19例，食管原位癌55例，食管浸润癌52例）中验证p-ERK1和p-ERK2蛋白的表达变化。结果在食管癌EC9706细胞中，ERK／MAPK信号通路呈高度活化状态。血清瞬时刺激10min后，p-ERK1和P—ERK2的表达达到峰值。EC9706细胞在50μmol／L的U0126处理下，p-ERK1和p-ERK2的表达几乎完全被抑制。t-ERK1 mRNA在25例哈萨克族食管癌患者肿瘤组织中的表达量为1．92±3．49，明显低于癌旁组织（3．67±7．47，P〈0．05）；t-ERK2 mRNA在食管癌组织和癌旁组织中的表达量差异无统计学意义（P〉0．05）。t-ERK1和t-ERK2蛋白在食管癌组织、相应癌旁组织和正常食管黏膜组织中的表达差异无统计学意义（P〉0．05）；但p-ERK1和p-ERK2蛋白在食管癌组织中的表达量（分别为0．87±0．14和0．79±0．10）均明显低于癌旁组织（分别为1．10±0．13和1.32±0．12，P〈0．05）和正常食管黏膜组织（分别为1．50±0．22和1．64±0．18，P〈0．05）。免疫组化染色验证的结果显示，p-ERK1和P—ERK2蛋白在浸润性食管癌组织中的阳性表达率均为7．7％（4／52），在癌旁正常食管黏膜组织中的阳性表达率均为31．6％�Objective To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma （ESCC） in Kazakh patients. Methods The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 （t-ERK1/2） and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR （qRT-PCR） and Western blotting, respectively. The expression of p-ERKI/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas. Results ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 μmoL/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67± 7.47 in the adjacent normal mucosa. The t-ERKI mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa （ P 〈 0.05 ）, whereas there was no significant difference of t-ERK2 mRNA level between them （P 〉 0.05 ）. The expression levels of p-ERK 1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ±0.13 and 1.32±0.12 in the adjacent normal mucosae, p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue （P 〈0.01 ）. However, there was no significant difference between their t-ERK1/2 protein levels （ P 〉 0.05 ）. In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal

关 键 词：食管肿瘤 哈萨克族 细胞外信号调节激酶/丝裂原活化蛋白激酶信号通路 

分 类 号：R735.1[医药卫生—肿瘤]