Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres

Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after auto phosphorylation of the epidermal growth factor receptor (EGFR), We examined if mineral fibres with known carcinogenicity can be discriminated from mat erials with less or no carcinogenicity by their ability to up-regulate expr ession of EGFR protein in RPM cells in vitro. Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were as sociated with increases in EGFR protein expression over sham controls, wher eas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Inten se patterns of EGFR protein expression were linked to RPM cells phagocytosi ng long fibres, To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell n uclear antigen (PCNA) in combination with an antibody against EGFR, In thes e co-localization studies, cells showed intense staining for EGFR protein 2 4 h before being PCNA positive at 48 h, These results suggest that carcinog enic fibres induce EGFR and initiate cell signalling cascades in mesothelia l cells, leading to cell proliferation and carcinogenesis.