Downmodulation of c- myc expression by interferon γ and tumour necrosis factor α precedes growth arrest in human melanoma cells

Abstract

After in vitro incubation of melanoma tumour cells Cme1453A with either recombinant interferon gamma (rIFN-γ) or tumour necrosis factor alpha (rTNF-α) a dose-dependent inhibition of cell growth occurred; when both cytokines were added, a synergistic action was observed. Inhibition of DNA synthesis, as measured by [ 3H] thymidine incorporation, occurred after 6 h of incubation with rIFN-γ or rTNF-α, and this action was potentiated when the two cytokines were applied simultaneously. Within 1 h, the level of c- myc mRNA in tumour cells had already decreased by, respectively, 60% (S.D. 7) and 25% (S.D. 7); the combined addition of the cytokines resulted in a greater reduction of c- myc mRNA than by each cytokine alone. Downregulation of c- myc expression is an early event, occurring hours before the actual inhibition of outgrowth. Thus, in melanoma cells like Cmel with a high constitutive expression of the c- myc oncogene, the antiproliferative action of rIFN-γ and rTNF-α may be mediated by an inhibition of the expression of c- myc.