c-Myc-mediated expression of nucleophosmin/B23 decreases during retinoic acid-induced differentiation of human leukemia HL-60 cells.
The retinoic acid-induced differentiation of human leukemia HL-60 cells towards mature granulocytic cells was accompanied by the decline in the protein levels of c-myc, nucleophosmin/B23 and its promoter activity. These RA-induced effects were further enhanced by the concurrent treatment of HL-60 cells with p38 map kinase inhibitor SB203580 (SB). It seems that there is a strong correlation of nucleophosmin/B23 and c-Myc expressions in cells under RA treatment. Furthermore, nucleophosmin/B23 promoter activity decreased upon c-Myc antisense-mediated reduction of intracellular amount of c-Myc. CHIP assays showed that binding of c-Myc to the nucleophosmin/B23 promoter decreased in RA-treated cells. Thus, nucleophosmin/B23 expression is targeted by c-Myc during RA-induced differentiation. These results provide evidence for a novel mechanism of transcriptional downregulation of nucleophosmin/B23 and the functional role of c-Myc in RA-induced differentiation.
Yung
Benjamin Y M
BY
Cancer Biochemistry Laboratory, Department of Pharmacology, College of Medicine, Chang Gung Genomics Research Center, Chang Gung University, Tao-Yuan 333, Taiwan, Republic of China. byung@mail.cgu.edu.tw
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D011725:Pyridines; D000090243:Nucleophosmin; D014212:Tretinoin; D048051:p38 Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate; C093642:SB 203580