title: Downmodulation of c-myc expression by interferon gamma and tumour necrosis factor alpha precedes growth arrest in human melanoma cells.
abstract: After in vitro incubation of melanoma tumour cells Cmel453A with either recombinant interferon gamma (rIFN-gamma) or tumour necrosis factor alpha (rTNF-alpha) 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-gamma or rTNF-alpha, 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-gamma and rTNF-alpha may be mediated by an inhibition of the expression of c-myc.
authors.affiliation: Department of Clinical Oncology, Leiden University Hospital, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Osanto
authors.forename: R
authors.initials: R
authors.lastname: Jansen
authors.forename: M
authors.initials: M
authors.lastname: Vloemans
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003513:Cycloheximide