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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

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Virchows Archiv B

Summary

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 cfos 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.

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Supported by the Deutsche Forschungsgemeinschaft (He 1380-2/ 1) and the Mildred Scheel Stiftung für Krebsforschung (to M.A.B.)

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Brach, M.A., Riedel, D., Mertelsmann, R. et al. 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. Virchows Archiv B Cell Pathol 59, 54–58 (1990). https://doi.org/10.1007/BF02899387

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  • DOI: https://doi.org/10.1007/BF02899387

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