ArticleWorld journal of gastroenterology2005
Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer.
Article in World journal of gastroenterology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review of microRNA expression profiling studies in human gastric cancer.Cancer medicine · 2014Pooled it
- Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD study.Investigational new drugs · 2013Trial
- Integrated Elementomics-Genomics-Metabolomics Analysis Reveals Plasma Biomarker Networks and Diagnostic Potential for Gastric Cancer.Metabolites · 2026Article
- A Narrative Review on Unravelling Bacterial-Mediated Carcinogenesis and Possible Alternative Treatment Strategies.BioMed research international · 2026Review
- Atypical MAPKs in cancer.The FEBS journal · 2025Review
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- Review
- FBXW7-mediated ERK3 degradation regulates the proliferation of lung cancer cells.Experimental & molecular medicine · 2022Article
- Increased CD44 Expression and MEK Activity Predict Worse Prognosis in Gastric Adenocarcinoma Patients Undergoing Gastrectomy.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2021Article
- miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6.Molecular medicine reports · 2021Article
- ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers.BMC cancer · 2021Article
- The prediction of survival in Gastric Cancer based on a Robust 13-Gene Signature.Journal of Cancer · 2021Article
- Pterostilbene enhances sorafenib's anticancer effects on gastric adenocarcinoma.Journal of cellular and molecular medicine · 2020Article
- A Novel Ten-Gene Signature Predicting Prognosis in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2020Article
- Down-regulation of lncRNA LINC00152 Suppresses Gastric Cancer Cell Migration and Invasion Through Inhibition of the ERK/MAPK Signaling Pathway.OncoTargets and therapy · 2020Article
- The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness.Journal of cellular physiology · 2019Article
- Poor expression of microRNA-135b results in the inhibition of cisplatin resistance and proliferation and induces the apoptosis of gastric cancer cells through MST1-mediated MAPK signaling pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Involvement of the long noncoding RNA NEAT1 in carcinogenesis.Molecular oncology · 2019Review
- Activation loop phosphorylation of ERK3 is important for its kinase activity and ability to promote lung cancer cell invasiveness.The Journal of biological chemistry · 2018Article
- The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture.The Journal of biological chemistry · 2018Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo 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.
methodsWestern 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.
resultsCompared 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.
conclusionMAPKs, 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.
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