Interferon alpha/beta modulation of growth-factor-stimulated mitogenicity in AKR-2B fibroblasts.
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.
Pietenpol
J A
JA
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Howe
P H
PH
Cunningham
M R
MR
Leof
E B
EB
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D006133:Growth Substances / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects
D006133:Growth Substances; D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors