This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Timblin, C. R. Articles by Mossman, B. T. Search for Related Content PubMed PubMed Citation Articles by Timblin, C. R. Articles by Mossman, B. T.

Transcriptional Activation of the Proto-oncogene c-jun by Asbestos and H₂O₂ Is Directly Related to Increased Proliferation and Transformation of Tracheal Epithelial Cells¹

Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont 05405

Asbestos causes persistent increases in c-jun mRNA and AP-1 DNA binding activity in hamster tracheal epithelial (HTE) cells, the progenitor cell type of asbestos-induced bronchogenic carcinoma. Studies here were designed to determine mechanisms of c-jun induction by asbestos and the phenotypic consequences of Jun expression in HTE cells. To examine whether asbestos or H₂O₂ induced transcription of c-jun, we transiently transfected HTE cells with a plasmid containing a fragment of the c-jun promoter coupled to a luciferase reporter gene. In addition, c-jun was overexpressed in cells using a full-length human c-jun construct, and effects on proliferation and transformation were examined. HTE cells transfected with the jun-luciferase construct showed increased luciferase activity when exposed to crocidolite asbestos or H₂O₂. These results demonstrate that asbestos and H₂O₂ activate AP-1-dependent gene transcription. Overexpression of c-jun led to increased proliferation and enhanced ability of HTE cells to grow in soft agar, an indication of cellular transformation. Data suggest that overexpression of c-jun may contribute to asbestos and oxidant-induced proliferation and carcinogenesis.

¹ This project was supported by Grant K01 OH00146 from the National Institute for Occupational Safety and Health of the Centers for Disease Control and Prevention (to C. R. T.), Grant RO1 06499 from the National Institute of Environmental Health Science (to B. T. M.), and Grant RO1 HL39469 from the National Heart, Lung & Blood Institute (to B. T. M.). Y. W. M. J. is a fellow of the Parker B. Francis Foundation.

² To whom requests for reprints should be addressed, at Department of Pathology, Medical Alumni Building, University of Vermont, Burlington, VT 05405-0068.

Received 4/18/95. Accepted 5/19/95.

This article has been cited by other articles:

				V. L. Kinnula, T. Torkkeli, P. Kristo, R. Sormunen, Y. Soini, P. Paakko, T. Ollikainen, K. Kahlos, A. Hirvonen, and S. Knuutila Ultrastructural and Chromosomal Studies on Manganese Superoxide Dismutase in Malignant Mesothelioma Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 147 - 153. [Abstract] [Full Text] [PDF]

				M. E. Ramos-Nino, L. Scapoli, M. Martinelli, S. Land, and B. T. Mossman Microarray Analysis and RNA Silencing Link fra-1 to cd44 and c-met Expression in Mesothelioma Cancer Res., July 1, 2003; 63(13): 3539 - 3545. [Abstract] [Full Text] [PDF]

				D. Upadhyay and D. W. Kamp Asbestos-Induced Pulmonary Toxicity: Role of DNA Damage and Apoptosis Experimental Biology and Medicine, June 1, 2003; 228(6): 650 - 659. [Abstract] [Full Text] [PDF]

				S. P. M. Reddy and B. T. Mossman Role and regulation of activator protein-1 in toxicant-induced responses of the lung Am J Physiol Lung Cell Mol Physiol, December 1, 2002; 283(6): L1161 - L1178. [Abstract] [Full Text] [PDF]

				M. E. Ramos-Nino, C. R. Timblin, and B. T. Mossman Mesothelial Cell Transformation Requires Increased AP-1 Binding Activity and ERK-dependent Fra-1 Expression Cancer Res., November 1, 2002; 62(21): 6065 - 6069. [Abstract] [Full Text] [PDF]

				C. B. Manning, A. B. Cummins, M. W. Jung, I. Berlanger, C. R. Timblin, C. Palmer, D. J. Taatjes, D. Hemenway, P. Vacek, and B. T. Mossman A Mutant Epidermal Growth Factor Receptor Targeted to Lung Epithelium Inhibits Asbestos-induced Proliferation and Proto-Oncogene Expression Cancer Res., August 1, 2002; 62(15): 4169 - 4175. [Abstract] [Full Text] [PDF]

				D. M. Flaherty, M. M. Monick, A. B. Carter, M. W. Peterson, and G. W. Hunninghake Oxidant-Mediated Increases in Redox Factor-1 Nuclear Protein and Activator Protein-1 DNA Binding in Asbestos-Treated Macrophages J. Immunol., June 1, 2002; 168(11): 5675 - 5681. [Abstract] [Full Text] [PDF]

				A. K. Hubbard, C. R. Timblin, M. Rincon, and B. T. Mossman Use of Transgenic Luciferase Reporter Mice To Determine Activation of Transcription Factors and Gene Expression by Fibrogenic Particles Chest, July 1, 2001; 120 (2009): 24S - 25S. [Full Text] [PDF]

				A. Shukla, C. R. Timblin, A. K. Hubbard, J. Bravman, and B. T. Mossman Silica-induced Activation of c-Jun-NH2-Terminal Amino Kinases, Protracted Expression of the Activator Protein-1 Proto-Oncogene, fra-1, and S-Phase Alterations Are Mediated via Oxidative Stress Cancer Res., March 1, 2001; 61(5): 1791 - 1795. [Abstract] [Full Text]

				A. Shukla, C. Timblin, K. BeruBe, T. Gordon, W. McKinney, K. Driscoll, P. Vacek, and B. T. Mossman Inhaled Particulate Matter Causes Expression of Nuclear Factor (NF)-kappa B-Related Genes and Oxidant-Dependent NF-kappa B Activation In Vitro Am. J. Respir. Cell Mol. Biol., August 1, 2000; 23(2): 182 - 187. [Abstract] [Full Text]

				C. L. Zanella, C. R. Timblin, A. Cummins, M. Jung, J. Goldberg, R. Raabe, T. R. Tritton, and B. T. Mossman Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L684 - L693. [Abstract] [Full Text] [PDF]

				Z. Sever-Chroneos, C. J. Bachurski, C. Yan, and J. A. Whitsett Regulation of mouse SP-B gene promoter by AP-1 family members Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L79 - L88. [Abstract] [Full Text] [PDF]

				D. W Kamp and S. A Weitzman The molecular basis of asbestos induced lung injury Thorax, July 1, 1999; 54(7): 638 - 652. [Full Text]

				K. Husgafvel-Pursiainen, A. Karjalainen, A. Kannio, S. Anttila, T. Partanen, A. Ojajärvi, and H. Vainio Lung Cancer and Past Occupational Exposure to Asbestos . Role of p53 and K-ras Mutations Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 667 - 674. [Abstract] [Full Text]

				M. Ding, J.-J. Li, S. S. Leonard, J.-P. Ye, X. Shi, N. H. Colburn, V. Castranova, and V. Vallyathan Vanadate-induced activation of activator protein-1: role of reactive oxygen species Carcinogenesis, April 1, 1999; 20(4): 663 - 668. [Abstract] [Full Text] [PDF]

				B. T. Mossman Review Article: Environmental Pathology: New Directions and Opportunities Toxicol Pathol, March 1, 1999; 27(2): 180 - 186. [Abstract] [PDF]

				R.-P. Huang, A. Peng, M. Z. Hossain, Y. Fan, A. Jagdale, and A. L. Boynton Tumor promotion by hydrogen peroxide in rat liver epithelial cells Carcinogenesis, March 1, 1999; 20(3): 485 - 492. [Abstract] [Full Text] [PDF]

				V. Lakshminarayanan, E. A. Drab-Weiss, and K. A. Roebuck H2O2 and Tumor Necrosis Factor-alpha Induce Differential Binding of the Redox-responsive Transcription Factors AP-1 and NF-kappa B to the Interleukin-8 Promoter in Endothelial and Epithelial Cells J. Biol. Chem., December 4, 1998; 273(49): 32670 - 32678. [Abstract] [Full Text] [PDF]

				L. A. Jimenez, C. Zanella, H. Fung, Y. M. W. Janssen, P. Vacek, C. Charland, J. Goldberg, and B. T. Mossman Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2 Am J Physiol Lung Cell Mol Physiol, November 1, 1997; 273(5): L1029 - L1035. [Abstract] [Full Text] [PDF]

				J. L. Goldberg, C. L. Zanella, Y. M. W. Janssen, C. R. Timblin, L. A. Jimenez, P. Vacek, D. J. Taatjes, and B. T. Mossman Novel Cell Imaging Techniques Show Induction of Apoptosis and Proliferation in Mesothelial Cells by Asbestos Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 265 - 271. [Abstract] [Full Text]

				B. T. MOSSMAN and A. CHURG Mechanisms in the Pathogenesis of Asbestosis and Silicosis Am. J. Respir. Crit. Care Med., May 1, 1997; 157(5): 1666 - 1680. [Full Text]