A DNA uptake-stimulating protein increases the antiproliferative effect of c-myb antisense oligonucleotide on leukemic cells

Authors

  • György Tóth,

    1. Department of Human Genetics, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • József Schlammadinger,

    1. Department of Human Genetics, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • János Aradi,

    1. Department of Biochemistry and Molecular Biology, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • Péter Antal-Szalmás,

    1. Department of Internal Medicine, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • Sándor Sipka,

    1. Department of Internal Medicine, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • Margit Balázs,

    1. School of Public Health, Department of Preventive Medicine, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • Péter Kovács,

    1. Semmelweis University, Department of Genetics, Cell and Immunobiology; Nagyvarad ter 4 1089, Budapest, Hungary
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  • Zsigmond Fehér,

    1. Department of Human Genetics, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary
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  • András Falus

    Corresponding author
    1. Semmelweis University, Department of Genetics, Cell and Immunobiology; Nagyvarad ter 4 1089, Budapest, Hungary
    2. Molecular Immunology Research Group, Hungarian Academy of Sciences, Budapest, Hungary
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Corresponding author: Semmelweis University, Department of Genetics, Cell and Immunobiology; Nagyvarad ter 4 1089, Budapest, Hungary. Tel.: +36 1 210 2929; fax: +36 1 303 6968. faland@dgci.sote.hu

Abstract

Proliferation of HL-60 and MOLT4 leukemia cells was inhibited by a c-myb antisense oligonucleotide (ASO) in the presence of a DNA uptake-stimulating protein (DNA uptake-stimulating factor, DUSF). The inhibitory effect was very mild in the absence of DUSF. Sense oligonucleotides or DUSF, alone or in combination, were found to be ineffective. Cellular expression of the c-myb protein was significantly more inhibited by the c-myb ASO in the presence than in the absence of DUSF. In the presence of DUSF, c-myb protein practically disappeared from the nuclei of HL-60 and MOLT4 cells treated with the ASO. Thus, DUSF appears to effectively stimulate the uptake of c-myb ASO into tumor cells in vitro, augmenting its antiproliferative effect by decreasing c-myb expression.

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