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.
Brach
M A
MA
Department of Hematology and Oncology, University of Freiburg, Federal Republic of Germany.
Riedel
D
D
Herrmann
F
F
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