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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 Cells

Transcriptional Activation of the Proto-Oncogene C-Jun by Asbestos and H2O2 Is Directly Related to Increased Proliferation and Transformation of Tracheal Epithelial Cells

C R Timblin, Y W Janssen, B T Mossman

Cancer Res. 1995 Jul 1;55(13):2723-6.

PMID: 7796393

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414966	C-jun, proto oncogene human			Price

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