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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.

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