Epidermal growth factor inhibits phosphoenolpyruvate carboxykinase gene expression in rat hepatocytes in primary culture.

Epidermal growth factor (EGF) decreased the basal, and blocked the dibutyryl cyclic AMP (Bt2cAMP)-induced, expression of P-enolpyruvate carboxykinase (GTP) (PEPCK) and tyrosine aminotransferase (TAT) genes in both rat hepatocytes in primary culture and the FTO-2B hepatoma cell line. Treatment of hepatocytes with EGF in combination with phorbol ester (TPA) resulted in an additive decrease of PEPCK mRNA levels. Overnight pretreatment of hepatocytes with TPA, which is known to downregulate protein kinase C, abolished the TPA and reduced the EGF-mediated inhibition of PEPCK gene expression. These results suggested that EGF caused its effect, at least in part, through protein kinase C.