Recombinant immune interferon down-regulates Ha-ras-1 proto-oncogene products in a human melanoma cell line.
The antiproliferative and antineoplastic effects of the interferons may result, at least in part, from changes in the expression and quantity of specific oncogene products. To explore this hypothesis we have determined the effect of interferons, including recombinant leukocyte (IFN-alpha), fibroblast (IFN-beta) and immune (IFN-gamma), on expression of the Ha-ras proto-oncogene in the human melanoma cell line Colo 38. While concentrations of up to 1000 U/ml of either IFN-alpha or IFN-beta did not affect the total amounts of Ha-ras products, IFN-gamma at concentrations ranging from 20 to 200 U/ml caused a dose- and time-dependent (48-96 hr) reduction (approximately 40%) in the accumulation of Ha-ras-1 mRNA and in the synthesis of the specific protein products. Downregulation of this proto-oncogene occurs prior to the antiproliferative effects of IFN-gamma and parallels similar IFN-gamma mediated changes in the expression of certain melanoma associated antigens. The present findings indicate that this experimental model may prove valuable in determining whether a direct relationship exists between the antiproliferative activity of specific interferons and the downregulation of oncogene expression.
Giacomini
P
P
Immunology Laboratory, Regina Elena Institute, Rome, Italy.
Gambari
R
R
Barbieri
R
R
Nastruzzi
C
C
Fraioli
R
R
Spandidos
D
D
Fisher
P B
PB
Natali
P G
PG
D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008545:Melanoma; D015689:Oncogene Protein p21(ras) / Q000032:analysis*; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D007371:Interferon-gamma; D015689:Oncogene Protein p21(ras)