Interferon alpha/beta modulation of growth-factor-stimulated mitogenicity in AKR-2B fibroblasts.

ABSTRACT

Growth factor-stimulated mitogenicity in mouse embryo-derived AKR-2B cells was inhibited in a dose-dependent fashion by a mixture of alpha and beta mouse interferons (IFN). A 60% decrease in epidermal growth factor (EGF) and insulin-stimulated DNA synthesis was observed with 10 kU/ml IFN, and half-maximal inhibition was seen at 1 kU/ml. Likewise, the mitogenic effect of 5% fetal bovine serum (FBS) was inhibited by 60% with 10 kU/ml IFN and by 38% with 1 kU/ml IFN. IFN inhibition of DNA synthesis was paralleled by a decrease in monolayer growth of AKR-2B cells by 60% on the 3rd day of culture and by 40% on the 6th day of culture. Soft agar growth of two AKR-2B derived lines, AKR-MCA and AKR-2B (clone 84A), was also inhibited significantly with the addition of 1-10 kU/ml of IFN. The effect of IFN on EGF receptors was also examined. Treatment of AKR-2B cells with 10 kU/ml IFN resulted in a 35% decrease in EGF binding to cell surface receptors. The reduced binding of EGF to cells treated with IFN was due to a loss of EGF receptors as determined by Scatchard analysis. IFN treatment of AKR-2B cells neither altered the affinity of the EGF receptor for its ligand nor affected receptor internalization. Nuclear transcription and actinomycin D decay analysis indicated that within 2 hr, IFN reduced c-myc messenger RNA levels at the level of transcription with no affect on message decay.