Hybrid recombinant human leukocyte interferon inhibits differentiation in murine B-16 melanoma cells.
We have investigated the effects of recombinant human leukocyte interferons (IFN-alpha A and IFN-alpha D) and various hybrid recombinant human leukocyte interferons on differentiation in B-16 mouse melanoma cells. Inhibition of both spontaneous and melanocyte hormone stimulated differentiation was observed with one hybrid construct, IFN-alpha A/D (Bgl) consisting of amino acids 1 to 62 from IFN-alpha A and amino acids 64 to 166 from IFN-alpha D. In contrast, the parental human interferons, IFN-alpha A and IFN-alpha D, when used alone or in combination, as well as other hybrid human leukocyte interferons, did not cause significant inhibition of melanogenesis in B-16 mouse cells. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) also inhibited B-16 differentiation and the combination of TPA with IFN-alpha A/D (Bgl) or mouse L-cell interferon was synergistic in delaying melanogenesis. These studies indicate that the IFN-alpha A/D (Bgl) hybrid that exhibits antiviral activity on mouse cells can also inhibit differentiation of murine cells.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004274:DNA, Recombinant; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology*; D007739:L Cells / Q000032:analysis; D008543:Melanins / Q000096:biosynthesis; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020798:Two-Hybrid System Techniques
D004274:DNA, Recombinant; D007370:Interferon Type I; D008543:Melanins; D009074:Melanocyte-Stimulating Hormones; D013755:Tetradecanoylphorbol Acetate