Transcription interruption may be a common mechanism of c-myc regulation during HL-60 differentiation.
Human promyelocytic leukemia cells (HL-60) differentiate along a monocytoid pathway in response to recombinant human tumor necrosis factor or recombinant human interferon gamma. Together, these agents act synergistically to induce phenotypic differentiation. Since reduced expression of mRNA for the proto-oncogene c-myc correlates with differentiation of HL-60 cells induced by other agents, we tested the abilities of tumor necrosis factor and interferon gamma to regulate expression of c-myc mRNA. Tumor necrosis factor rapidly and effectively reduced c-myc mRNA levels. In contrast, interferon gamma did not affect c-myc mRNA levels, nor did it show synergy with tumor necrosis factor in reducing c-myc. Transcription run-on studies confirmed that tumor necrosis factor caused interruption of c-myc transcription after exon 1. Phorbol diesters also caused interruption of transcription of c-myc. Thus, interruption of transcription may be a common mode of regulation of c-myc during induced differentiation of HL-60 cells.
D002454:Cell Differentiation / Q000187:drug effects; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D010703:Phorbol Esters / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C000715470:MAS1 protein, human; D010703:Phorbol Esters; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma