The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis
Abstract
We examined the mechanisms of interaction of crocidolite asbestos fibers with the epidermal growth factor (EGF) receptor (EGFR) and the role of the EGFR-extracellular signal-regulated kinase (ERK) signaling pathway in early-response protooncogene (c- fos/c- jun) expression and apoptosis induced by asbestos in rat pleural mesothelial (RPM) cells. Asbestos fibers, but not the nonfibrous analog riebeckite, abolished binding of EGF to the EGFR. This was not due to a direct interaction of fibers with ligand, inasmuch as binding studies using fibers and EGF in the absence of membranes showed that EGF did not adsorb to the surface of asbestos fibers. Exposure of RPM cells to asbestos caused a greater than twofold increase in steady-state message and protein levels of EGFR ( P < 0.05). The tyrphostin AG-1478, which inhibits the tyrosine kinase activity of the EGFR, but not the tyrphostin A-10, which does not affect EGFR activity, significantly ameliorated asbestos-induced increases in mRNA levels of c- fos but not of c- jun. Pretreatment of RPM cells with AG-1478 significantly reduced apoptosis in cells exposed to asbestos. Our findings suggest that asbestos-induced binding to EGFR initiates signaling pathways responsible for increased expression of the protooncogene c- fos and the development of apoptosis. The ability to block asbestos-induced elevations in c- fos mRNA levels and apoptosis by small-molecule inhibitors of EGFR phosphorylation may have therapeutic implications in asbestos-related diseases.
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“A number of in vitro and in vivo studies have suggested that shape, cristallinity, chemical composition and durability are important factors accounting for the biological activities of fibers, especially their carcinogenic potency.”
From Quantification of short and long asbestos fibers to assess asbestos exposure: A review of fiber size toxicity (2014) · cites this paper as [93]
In the citing paper
“Comparison between the biological effects of asbestos and non-fibrous particles of similar chemical composition, such as crocidolite and riebeckite, has demonstrated a greater potency of the fibrous counterparts to produce apoptosis, oxidative DNA damage, DNA breakage and to induce proto-oncogene expression [88-93].”
From Quantification of short and long asbestos fibers to assess asbestos exposure: A review of fiber size toxicity (2014) · cites this paper as [93]
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Self-citation
Metadata
- Authors
- Zanella, C. L., Timblin, C. R., Cummins, A., Jung, M., Goldberg, J., Raabe, R., Tritton, T. R., & Mossman, B. T.
- Affiliations
- Departments of Pathology and
- Pharmacology, University of Vermont College of Medicine, Burlington, Vermont 05405
- Venue
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Publisher
- American Physiological Society
- Published
- 1999-10-01
- Volume
- 277
- Issue
- 4
- Pages
- L684-L693
- ISSN
- 1040-0605
- 1522-1504
- Cited by
- 38
- References
- 51
- Language
- en
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