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 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.
Faux
S P
SP
MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK.
Houghton
C E
CE
Hubbard
A
A
Patrick
G
G
D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D017632:Asbestos, Serpentine / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010994:Pleura / Q000166:cytology*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation; D017641:Zeolites / Q000633:toxicity*
D017632:Asbestos, Serpentine; D002273:Carcinogens; D017638:Asbestos, Crocidolite; C083174:erionite; D017641:Zeolites; D066246:ErbB Receptors