title: Ciprofibrate, a carcinogenic peroxisome proliferator, increases the phosphorylation of epidermal-growth-factor receptor in isolated rat hepatocytes.
abstract: Ciprofibrate, a hypolipidaemic drug with carcinogenic and peroxisome-proliferation effects in rat liver, was found to increase the phosphorylation of epidermal-growth-factor receptor in 32P-labeled isolated rat hepatocytes. This effect was suppressed by protein-kinase-C inhibitors, and was accompanied by an almost complete inhibition of the receptor autophosphorylation normally induced by its ligand. However, in vitro experiments showed that protein-kinase-C phosphorylation of purified epidermal-growth-factor receptor was activated by ciprofibroyl-CoA, the acyl-CoA derivative of the drug, but not by the unmodified drug. Neither compound affected the ligand induction of epidermal-growth-factor-receptor autophosphorylation in isolated liver membranes. These results suggest that metabolically produced ciprofibroyl-CoA in liver cells would activate protein-kinase-C and produce changes in epidermal-growth-factor-receptor function.
authors.affiliation: Facultad de Ciencias Biológicas, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago.
authors.forename: A
authors.initials: A
authors.lastname: Orellana
authors.forename: L
authors.initials: L
authors.lastname: Holuigue
authors.forename: P C
authors.initials: PC
authors.lastname: Hidalgo
authors.forename: V
authors.initials: V
authors.lastname: Faúndez
authors.forename: A
authors.initials: A
authors.lastname: González
authors.forename: M
authors.initials: M
authors.lastname: Bronfman
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D058607:Fibric Acids; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008830:Microbodies / Q000187:drug effects*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
chemical_list: D000214:Acyl Coenzyme A; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D002995:Clofibric Acid; D066246:ErbB Receptors; D011493:Protein Kinase C; C019304:ciprofibrate