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.