Phenobarbital decreases hepatocyte EGF receptor expression independent of protein kinase C activation.
The liver tumor promoter, phenobarbital, directly applied to cultured, adult rat hepatocytes at concentrations of greater than 1 mM, decreases cellular surface binding of EGF. This effect of phenobarbital resembles that of 4 beta-phorbol-12 alpha-myristate-13 beta-acetate (TPA) in that both decrease EGF receptor number, but do not affect receptor affinity. The effects of the two tumor promoters differ however, in that only TPA reduces high affinity EGF binding by A431 cells. They also differ in that TPA, but not phenobarbital, causes redistribution of protein kinase C from a soluble to a membranous hepatocyte subcellular fraction. These data indicate that decreased EGF binding is a common hepatocyte response to the tumor promoters, TPA and phenobarbital, but that this response can be mediated by either a TPA-activated, protein kinase C-dependent pathway or by a phenobarbital-sensitive, protein kinase C-independent pathway.
Department of Radiology, Duke University Medical Center, Durham, N.C. 27710.
S A
SA
Meyer
R L
RL
Jirtle
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D010634:Phenobarbital