Effects of interferon-gamma on proto-oncogene expression during induction of human monocytic differentiation.
Activation of the proto-oncogenes c-fos, c-fms, and c-sis has been associated with monocytic differentiation. In the present study, we monitored the relationship of c-myc, c-fos, c-fms, and c-sis expression to interferon-gamma (IFN-gamma)-induced monocytic differentiation of human HL-60 promyelocytic leukemia cells. Treatment of HL-60 cells with 500 U/ml IFN-gamma arrested cell proliferation after 3 days. Appearance of the monocytic phenotype was manifested within 24 hr of IFN-gamma exposure by: increased nitroblue tetrazolium reduction; increased cell surface expression of the HLA-DR, Mo1, and MY4 antigens; and induction of transcripts for the second component of complement (C2) and tumor necrosis factor. In contrast, c-myc expression decreased as a later event after 72 hr of IFN-gamma exposure, and c-fos transcripts remained undetectable until 5 days of treatment. Furthermore, c-fms RNA and transcripts for the macrophage marker apolipoprotein E were induced only after 7 days. Finally, expression of the c-sis proto-oncogene at the RNA and protein levels remained undetectable after induction with IFN-gamma. These findings would thus suggest that declines in c-myc RNA, as well as induction of c-fos, c-fms, and c-sis expression, are not requisite events in the commitment of HL-60 cells to IFN-gamma-induced monocytic differentiation. Expression of c-fos and c-fms, however, is associated with acquisition of markers associated with maturation to macrophages.
D000954:Antigens, Surface / Q000032:analysis; D001057:Apolipoproteins E / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D000954:Antigens, Surface; D001057:Apolipoproteins E; D006023:Glycoproteins; D006684:HLA-DR Antigens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate