title: Granulocytic differentiation of HL-60 cells, both spontaneous and drug-induced, might require loss of extrachromosomal DNA encoding a gene(s) not c-MYC.
abstract: Treatment of HL-60 cells with drugs induces granulocytic differentiation and c-MYC down-regulation that is irreversible and associated with loss of DNase I-hypersensitive sites in c-MYC promoter. The expression of these phenotypes requires a slow process that appears to accompany a loss of c-MYC copies in double minutes via micronuclei. However, the drug treatment induced c-MYC down-regulation very early, though only reversibly. Here we show that we can resolve this paradox by assuming a gene(s) in other extrachromosomal, acentromeric DNA. Treatment with drugs might induce no down-regulation of this gene, but its complete elimination via micronuclei might be necessary and sufficient for the expression of the above phenotypes. Loss of c-MYC copies is unavoidable because the exclusion of extrachromosomal DNAs via micronuclei is at random. This conclusion is based on the observation of a substantial number of c-MYC copies in certain differentiated cells, irrespective of whether the differentiation was induced with drugs or without.
authors.affiliation: Life Science Group, Faculty of Integrated Art and Sciences, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8521, Japan.
authors.forename: M M
authors.initials: MM
authors.lastname: Haque
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Utiyama
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D006098:Granulocytes / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*
chemical_list: D016271:Proto-Oncogene Proteins c-myc