Changes in Topoisomerase I Levels and Localization during Myeloid Maturation in Vitro and in Vivo

Scott H. Kaufmann, Martin Charron, Philip J. Burke, Judith E. Karp, Scott H. Kaufmann

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Changes in topoisomerase I (topo I) levels and localization were examined during the course of granulocytic maturation in vitro and in vivo. Western blotting revealed that granulocytic maturation in DMSO-treated HL-60 human leukemia cells was accompanied by a 5-fold decrease in topo I polypeptide content Consistent with this result, 3- to 5-fold higher concentrations of the topo I poison camptothecin were required to stabilize topo I-DNA adducts in DMSO-treated HL-60 cells compared to untreated cells. Northern blotting revealed that these changes occurred without any decrease in topo I message. Immunolocalization studies revealed that these quantitative changes were accompanied by redistribution of topo I away from the nucleoli, where it was prominently accumulated in untreated HL-60 cells, to a more uniform nuclear distribution in DMSO-treated cells. Similar changes occurred during granulocytic maturation in human marrow in vivo. Western blotting revealed that topo I levels in normal progranulocytes were 50% as high as those in HL-60 cells, levels in metamyelocytes were 35% as high as HL-60 cells, and levels in peripheral blood granulocytes were 5% as high as HL-60 cells. Two other polypeptides that are concentrated in nucleoli, poly(ADP-ribose) polymerase and B23/nucleophosmin, also decreased during the course of granulocytic maturation. These changes were accompanied by an alteration in topo I localization similar to that observed in HL-60 cells during the course of granulocytic maturation. Conversely, treatment of human lymphocytes with the mitogenic lectin concanavalin A resulted in a 3-fold increase in topo I polypeptide content concomitant with a prominent increase in the amount of nucleolar antigen. These observations not only provide a context for understanding the recent observation that topo I levels are higher in human leukemia specimens than in normal marrow but also raise the possibility that elevated topo I levels in other cells might reflect alterations in nucleolar structure and function.

Original languageEnglish (US)
Pages (from-to)1255-1260
Number of pages6
JournalCancer research
Volume55
Issue number6
StatePublished - Mar 15 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kaufmann, S. H., Charron, M., Burke, P. J., Karp, J. E., & Kaufmann, S. H. (1995). Changes in Topoisomerase I Levels and Localization during Myeloid Maturation in Vitro and in Vivo. Cancer research, 55(6), 1255-1260.