title: Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription.
abstract: Highly purified, recombinant human tumor necrosis factor type alpha (rTNF-alpha) exerts cytostatic activity on the human promyelocytic leukemic cell line HL-60. Between 4 and 10 hr after treatment with rTNF-alpha, HL-60 cells start to exhibit phagocytic activity, indicating the induction of a differentiation process, and show a marked decline in steady-state levels of MYC mRNA. In vitro transcription assays reveal that rTNF-alpha inhibits MYC gene expression at the level of transcription. rTNF-alpha has little or no effect on the half-life of MYC mRNA, indicating that the decreased MYC mRNA level is primarily due to reduced transcription, and the protein synthesis inhibitor cycloheximide does not prevent rTNF-alpha-mediated inhibition of MYC gene expression, suggesting that rTNF-alpha action is independent of de novo protein synthesis. In contrast to MYC, HLA-A, -B, -C mRNA levels are slightly increased in rTNF-alpha-treated HL-60 cells. Recombinant interferon-gamma, which also enhances HLA gene transcription in HL-60 cells, fails to reduce MYC mRNA levels and lacks cytostatic activity. Attenuation of HL-60 cell proliferation occurs as a late response to treatment with rTNF-alpha and thus may be secondary to both MYC inhibition and induction of cell differentiation.
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000502:physiology*; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007700:Kinetics; D009857:Oncogenes; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D006131:Growth Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma