Zheng Shu-tao, Liu Tao, Middottuersun Aerziguli, Huo Qi, Liu Qing, Huang Cong-gai, Feng Jun-guo, Lü Guo-dong, Wang Xing, Lin Ren-Yong, Sheyhidin Ilyar, Lu Xiao-Mei
Medical Research Center, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830054, China.
Zhonghua Zhong Liu Za Zhi. 2011 Jun;33(6):421-5.
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.
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-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas.
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-ERK1 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-ERK1 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 cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05).
ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.
探讨ERK1/2丝裂原活化蛋白激酶（MAPK）信号转导通路在哈萨克族食管癌患者发病机制中的表达变化及意义。
采用蛋白质免疫印迹法检测血清饥饿及U0126抑制剂处理后食管癌EC9706细胞系中p-ERK1/2的表达水平。分别采用实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测并鉴定25对哈萨克族食管癌患者癌组织及癌旁正常食管黏膜组织中总ERK1/2（t-ERK1/2）的mRNA水平、t-ERK1/2及p-ERK1/2蛋白的表达水平。采用免疫组织化学法在126例石蜡包埋标本中验证p-ERK1/2蛋白的表达情况，其中包括19例正常食管黏膜、55例原位癌和52例浸润癌。
ERK1/2 MAPK信号转导通路在EC9706细胞中处于激活状态。瞬时血清刺激后10分钟，EC9706细胞中p-ERK1/2的表达水平达到峰值，50 μmol/L U0126处理后p-ERK1/2的表达完全受到抑制。在25对食管癌及癌旁正常黏膜中，癌组织中t-ERK1 mRNA水平为1.92±3.49，癌旁正常黏膜中为3.67±7.47。癌组织中t-ERK1 mRNA水平显著低于癌旁正常黏膜（P<0.05），而两者之间t-ERK2 mRNA水平差异无统计学意义（P>0.05）。癌组织中p-ERK1和p-ERK2蛋白的表达水平分别为0.87±0.14和0.79±0.10，癌旁正常黏膜中分别为1.10±0.13和1.32±0.12。癌组织中p-ERK1/2蛋白显著低于癌旁正常组织（P<0.01）。然而，两者之间t-ERK1/2蛋白水平差异无统计学意义（P>0.05）。在126例石蜡包埋标本中，食管癌组织中p-ERK1和p-ERK2的阳性表达率均为7.7%（4/52），显著低于癌旁正常黏膜（31.6%，6/19）和原位癌（85.5%，47/55，P<0.05）。
ERK1/2 MAPK信号通路在食管癌及癌旁正常黏膜中处于激活状态。我们的结果提示，p-ERK1/2 MAPK信号转导通路的激活在哈萨克族食管癌患者发病机制的早期阶段发挥作用。
