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. 1987 Jan;84(2):469–473. doi: 10.1073/pnas.84.2.469

Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription.

M Krönke, C Schlüter, K Pfizenmaier
PMCID: PMC304229  PMID: 3099296

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.

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