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-α), fibroblast (IFN-β) and immune (IFN-γ), 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-α or IFN-β did not affect the total amounts of Ha-ras products, IFN-γ 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-γ and parallels similar IFN-γ 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.
|Number of pages||7|
|Publication status||Published - 1990|
- Ha-ras-1 Expression
ASJC Scopus subject areas
- Cancer Research