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Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer
Liang, Bin1,2; Wang, Shan1,2; Zhu, Xue-Guang1,2; Yu, Yong-Xiang1,2; Cui, Zhi-Rong1,2; Yu, You-Zhi3
关键词Gastric Cancer Mitogen-activated Protein Kinase Extracellular Signal-regulated Kinase Signal Transduction
刊名WORLD JOURNAL OF GASTROENTEROLOGY
2005-02-07
11期:5页:623-628
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Gastroenterology & Hepatology
资助者Technology Foundation of Ministry of Education, China ; Technology Foundation of Ministry of Education, China
研究领域[WOS]Gastroenterology & Hepatology
英文摘要

AIM: To investigate the expression of mitogen-activated protein kinases (MAPKs) and its upstream protein kinase in human gastric cancer and to evaluate the relationship between protein levels and clinicopathological parameters.

METHODS: Western blot was used to measure the expression of extracellular signal-regulated kinase (ERK)-1, ERK-2, ERK-3, p38 and mitogen or ERK activated protein kinaseMEK-1 proteins in surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 42 patients. Immunohistochemistry was employed for their localization.

RESULTS: Compared with normal tissues, the protein levels of ERK-1 (integral optical density value 159 526 +/- 65 760 vs 122 807 +/- 65 515, P = 0.001), ERK-2 (168 471 +/- 95 051 vs 120 469 +/- 72 874, P<0.001), ERK-3 (118 651 +/- 71 513 vs 70 934 +/- 68 058, P<0.001), P38 (104 776 +/- 51 650 vs 82 930 +/- 40 392, P = 0.048) and MEK-1 (116 486 +/- 45 725 vs 101 434 +/- 49 387, P = 0.027) were increased in gastric cancer tissues. Overexpression of ERK-3 was correlated to TNM staging [average ratio of integral optic density (IOD)(tumor): IOD(normal) in TNM I, II, III, IV tumors was 1.43 +/- 0.34, 5.08 +/- 3.74, 4.99 +/- 1.08, 1.44 +/- 1.02, n = 42, P = 0.023] and serosa invasion (4.31 +/- 4.34 vs 2.00 +/- 2.03, P = 0.037). In poorly differentiated cancers (n = 33), the protein levels of ERK-1 and ERK-2 in stage III and IV tumors were higher than those in stage I and II tumors (2.64 +/- 3.01 vs 1.01 +/- 0.33, P = 0.022; 2.05 +/- 1.54 vs 1.24 +/- 0.40, P = 0.030). Gastric cancer tissues with either lymph node involvement (2.49 +/- 2.91 vs 1.03 +/- 0.36, P = 0.023; 1.98 +/- 1.49 vs 1.24 +/- 0.44, P = 0.036) or serosa invasion (2.39 +/- 2.82 vs 1.01 +/- 0.35, P = 0.022; 1.95 +/- 1.44 vs 1.14 +/- 0.36, P = 0.015) expressed higher protein levels of ERK-1 and ERK-2. In Borrmann II tumors, expression of ERK-2 and ERK-3 was increased compared with Borrmann III tumors (2.57 +/- 1.86 vs 1.23 +/- 0.60, P = 0.022; 5.50 +/- 5.05 vs 1.83 +/- 1.21, P = 0.014). Borrmann IV tumors expressed higher p38 protein levels. No statistically significant difference in expression of MAPKs was found when stratified to tumor size or histological grade (P>0.05). Protein levels of ERK-2, ERK-3 and MEK-1 in metastatic lymph nodes were 2-7 folds higher than those in adjacent normal mucosa. The immunohistochemistry demonstrated that ERK-1, ERK-2, ERK-3, p38 and MEK-1 proteins were mainly localized in cytoplasm. The expression of MEK-1 in gastric cancer cells metastasized to lymph nodes was higher than that of the primary site.

CONCLUSION: MAPKs, particularly ERK subclass are overexpressed in the majority of gastric cancers. Overexpression of ERKs is correlated to TNM staging, serosa invasion, and lymph node involvement. The overexpression of p38 most likely plays a prominent role in certain morphological subtypes of gastric cancers. MEK-1 is also overexpressed in gastric cancer, particularly in metastatic lymph nodes. Upregulation of MAPK signal transduction pathways may play an important role in tumorigenesis and metastatic potential of gastric cancer. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

语种英语
资助者Technology Foundation of Ministry of Education, China ; Technology Foundation of Ministry of Education, China
WOS记录号WOS:000208100100002
引用统计
被引频次:46[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55480
专题北京大学第二临床医学院
作者单位1.Peking Univ, Peoples Hosp, Div Surg Oncol, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp, Div Gastrointestinal Surg, Beijing 100044, Peoples R China
3.Peking Univ, Peoples Hosp, Div Pathol, Beijing 100044, Peoples R China
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GB/T 7714
Liang, Bin,Wang, Shan,Zhu, Xue-Guang,et al. Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2005,11(5):623-628.
APA Liang, Bin,Wang, Shan,Zhu, Xue-Guang,Yu, Yong-Xiang,Cui, Zhi-Rong,&Yu, You-Zhi.(2005).Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer.WORLD JOURNAL OF GASTROENTEROLOGY,11(5),623-628.
MLA Liang, Bin,et al."Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer".WORLD JOURNAL OF GASTROENTEROLOGY 11.5(2005):623-628.
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