TY - JOUR AU - Stephen P. Faux, Catherine E. Houghton, Andrew Hubbard, Graham Patrick AB - Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after autophosphorylation of the epidermal growth factor receptor (EGFR). We examined if mineral fibres with known carcinogenicity can be discriminated from materials with less or no carcinogenicity by their ability to up-regulate expression of EGFR protein in RPM cells in vitro . Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were associated with increases in EGFR protein expression over sham controls, whereas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Intense patterns of EGFR protein expression were linked to RPM cells phagocytosing long fibres. To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell nuclear antigen (PCNA) in combination with an antibody against EGFR. In these co-localization studies, cells showed intense staining for EGFR protein 24 h before being PCNA positive at 48 h. These results suggest that carcinogenic fibres induce EGFR and initiate cell signalling cascades in mesothelial cells, leading to cell proliferation and carcinogenesis. Key words AP-1, activator protein-1 BSA, bovine serum albumin CLSM, confocal laser-scanning microscopy CMFPBS, calcium- and magnesium-free phosphate buffered saline EGFR, epidermal growth factor receptor FBS, fetal bovine serum MAP, mitogen-activated protein NF-κB, nuclear factor-κB NIEHS, National Institute of Environmental Health Services PCNA, proliferating cell nuclear antigen RPM, rat pleural mesothelial TNFα, tumour necrosis factor α TPA, phorbol 12-myristate 13-acetate UICC, Unione International Centre le Cancer. © Oxford University Press « Previous | Next Article » Table of Contents This Article Carcinogenesis (2000) 21 (12): 2275-2280. doi: 10.1093/carcin/21.12.2275 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free A correction has been published Classifications Carcinogenesis Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Faux, S. 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