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PMID: 12711607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor alpha-converting enzyme and amphiregulin.

The Journal of biological chemistry ·Vol. 278 ·No. 28 ·2003-07-11 ·Pages 26202-7

Lemjabbar H, Li D, Gallup M, Sidhu S, Drori E, Basbaum C

Abstract

Cells dividing at the time of carcinogen exposure are at particular risk for neoplasia. Tobacco smoke contains numerous carcinogens, and we find that smoke, in the absence of exogenous growth factors, is capable of stimulating cell proliferation. The smoke-triggered mechanism includes the generation of oxygen radicals, which in turn stimulate tumor necrosis factor alpha-converting enzyme (a disintegrin and metalloproteinase (ADAM) 17) to cleave transmembrane amphiregulin, a ligand for the epidermal growth factor receptor (EGFR). The binding of amphiregulin to EGFR then stimulates proliferation of lung epithelial cells. These results shed light on the pathogenesis of lung cancer, suggest novel drug targets for the reduction of cancer risk in smokers, and provide insight into how EGFR integrates responses to diverse noxious stimuli.

MeSH Terms

ADAM Proteins ADAM17 Protein Amphiregulin Animals Carcinogens Cell Division/drug effects Cell Line Cells, Cultured Dose-Response Relationship, Drug EGF Family of Proteins Epithelial Cells/metabolism ErbB Receptors/metabolism Glycoproteins/metabolism Humans Immunoblotting Intercellular Signaling Peptides and Proteins/metabolism Ligands Lung/cytology,drug effects Lung Neoplasms/pathology Metalloendopeptidases/metabolism Mice Mice, Inbred C57BL Microscopy, Fluorescence Models, Biological Oligonucleotides, Antisense/pharmacology Oxygen/metabolism Phosphorylation Precipitin Tests Protein Binding Reactive Oxygen Species Smoking Tumor Cells, Cultured

Chemicals

AREG protein, human Amphiregulin Areg protein, mouse Carcinogens EGF Family of Proteins Glycoproteins Intercellular Signaling Peptides and Proteins Ligands Oligonucleotides, Antisense Reactive Oxygen Species ErbB Receptors ADAM Proteins Metalloendopeptidases ADAM17 Protein ADAM17 protein, human Adam17 protein, mouse Oxygen

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Lemjabbar Hassan

Biomedical Sciences Program, Cardiovascular Research Institute and Department of Anatomy, University of California, San Francisco, California 94143, USA.

Li Daizong

Gallup Marianne

Sidhu Sukhvinder

Drori Ehud

Basbaum Carol

Article Info

Journal

The Journal of biological chemistry

Abbr.

J Biol Chem

ISSN

0021-9258

DOI

10.1074/jbc.M207018200

Published

2003-07-11

Epub

2003-00-23

Pages

26202-7

Language

English

Region

United States

NLM ID

2985121R

Subset

Grants

NHLBI NIH HHS · P0-1 HL24136 · United States

NHLBI NIH HHS · R0-1 HL43762 · United States

External Links

PubMed source DOI: 10.1074/jbc.M207018200 View journal details

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Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor alpha-converting enzyme and amphiregulin.

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