Document Detail


Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF.
MedLine Citation:
PMID:  12099696     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Helicobacter pylori has a major aetiological role in human gastric carcinogenesis but the cellular and molecular pathways by which infection promotes transformation remain to be resolved. This study demonstrates that H. pylori exposure to MKN-1, ST42, and MKN-28 gastric epithelial tumour cells results in the activation of HB-EGF gene expression and EGFR tyrosine phosphorylation. These cell responses are induced by both cagPAI positive and cagPAI negative H. pylori strains and are dependent on cell surface expression of the HB-EGF precursor. The induction of HB-EGF gene transcription by H. pylori requires metalloprotease-, EGFR-, and Mek1-activities, indicating the involvement of the "triple membrane passing signal" (TMPS) for EGFR transactivation. Moreover, the release of the inflammatory cytokine IL-8 by cells exposed to H. pylori is significantly impaired by inhibitors of TMPS pathway elements. Our findings support a model in which H. pylori triggers constitutive EGFR signal activation, which enhances IL-8 production, and initiates neoplastic transformation of gastric epithelial cells.
Authors:
C Wallasch; J E Crabtree; D Bevec; P A Robinson; H Wagner; A Ullrich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  295     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-08     Completed Date:  2002-08-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  695-701     Citation Subset:  IM    
Copyright Information:
(c) 2002 Elsevier Science (USA).
Affiliation:
Axxima Pharmaceuticals AG, Am Klopferspitz 19, 82152 Martinsried, Germany. wallasch@axxima.com
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MeSH Terms
Descriptor/Qualifier:
Blotting, Northern
Blotting, Western
Cell Line
Cell Membrane / enzymology
Cells, Cultured
Coculture Techniques
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay
Epidermal Growth Factor / metabolism*
Epithelium / pathology
Helicobacter pylori / metabolism*
Humans
Intercellular Signaling Peptides and Proteins
Interleukin-8 / metabolism
Metalloendopeptidases / metabolism*
Phosphorylation
RNA, Messenger / metabolism
Receptor, Epidermal Growth Factor / genetics*,  metabolism*
Signal Transduction
Stomach / pathology
Stomach Neoplasms / enzymology
Time Factors
Transcriptional Activation*
Tyrosine / metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-8; 0/RNA, Messenger; 149176-25-0/heparin-binding EGF-like growth factor; 55520-40-6/Tyrosine; 62229-50-9/Epidermal Growth Factor; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.4.24.-/Metalloendopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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