| Helicobacter pylori-stimulated EGF receptor transactivation requires metalloprotease cleavage of HB-EGF. | |
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MedLine Citation:
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PMID: 12099696 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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C Wallasch; J E Crabtree; D Bevec; P A Robinson; H Wagner; A Ullrich |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 295 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-08 Completed Date: 2002-08-13 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 695-701 Citation Subset: IM |
Copyright Information:
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(c) 2002 Elsevier Science (USA). |
Affiliation:
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Axxima Pharmaceuticals AG, Am Klopferspitz 19, 82152 Martinsried, Germany. wallasch@axxima.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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