Induction of monocytic differentiation and modulation of the expression of c-fos, c-fms and c-myc protooncogenes in human monoblasts by cytokines and phorbolester.
Growing evidence suggests that proto-oncogenes regulate central aspects of cellular physiology such as cell proliferation and differentiation. The proto-oncogenes c-fos, c-fms and c-myc are thought to be involved in these processes. In this study the human myelomonoblast line THP-1 has been used to study monocytic differentiation in response to various cytokines and the phorbolester TPA. After treatment of THP-1 cells with Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL-6) and TPA the cells became adherent, lost their division potential and expressed new surface structures associated with monocytic differentiation. The expression of c-fos and c-fms transcripts was rapidly induced within 45 min by these agents and declined to undectable levels within 24 h. Exposure of THP-1 to TNF-alpha, IL-6 and TPA was associated with a rapid downregulation of c-myc expression, that returned to starting levels within 36 h. However, treatment of THP-1 with other cytokines including Granulocyte (G)-, Macrophage (M)-, Granulocyte/Macrophage (GM)-Colony Stimulating Factor (CSF), Interleukin (IL)-3 and Interleukin (IL)-4 failed to result in monocytic differentiation. These data suggest that changes in c-fms, c-myc and c-fos expression may be related to induction of monocytic differentiation and that their appearance or downregulation can be induced by certain cytokines.
Department of Hematology and Oncology, University of Freiburg, Federal Republic of Germany.
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MA
Brach
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Riedel
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Herrmann
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000276:immunology; D001685:Biological Factors / Q000494:pharmacology*; D018845:CD11 Antigens; D002454:Cell Differentiation; D016207:Cytokines; D015870:Gene Expression; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis; D016186:Receptor, Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D001685:Biological Factors; D018845:CD11 Antigens; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016186:Receptor, Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate