Transcriptional activation of the proto-oncogene c-jun by asbestos and H2O2 is directly related to increased proliferation and transformation of tracheal epithelial cells.

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.