Prostaglandins E2 and F2a mediate the increase in c-myc expression induced by EGF in primary rat hepatocyte cultures.
Epidermal Growth Factor (EGF) and prostaglandins (PGs) E2 and F2a, have been shown to stimulate primary hepatocyte proliferation. Verapamil (5-20 microM), a calcium channel inhibitor, inhibited hepatocyte DNA synthesis and c-myc expression, induced by EGF (50 ng/dish) and prostaglandins (1-12 micrograms/dish). Indomethacin (20-100 microM) decreased significantly the EGF-induced hepatocyte DNA synthesis and c-myc expression. Addition of PGs (1-9 micrograms) in hepatocyte cultures treated with EGF+indomethacin (100 microM) restored the capacity of EGF to increase c-myc expression and DNA synthesis. We propose that arachidonic acid derivatives and calcium channel blockers modulate c-myc expression in primary hepatocytes.
Skouteris
G G
GG
Department of Pathology, Duke University Medical Center, Durham, N.C. 27710.
Kaser
M R
MR
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D016271:Proto-Oncogene Proteins c-myc; D004815:Epidermal Growth Factor; D012313:RNA; D015237:Dinoprost; D014700:Verapamil; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine