Proceedings of the National Academy of Sciences of the United States of America
Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation--features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by northern blot analyses for c-myc mRNA levels in HTE cells. Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.
Janssen, Yvonne M.; Barchowsky, Aaron; Treadwell, Melinda; Driscoll, Kevin E.; and Mossman, B T., "Asbestos Induces Nuclear Factor Kappa B (NF-kappa B) DNA-Binding Activity and NF-Kappa B-Dependent Gene Expression in Tracheal Epithelial Cells." (1995). Open Dartmouth: Faculty Open Access Articles. 1622.