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Anti-c-myc DNA increases differentiation and decreases colony formation by HL-60 cells

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Summary

The proto-oncogene c-myc, whose gene product has a role in replication, is overexpressed in the human promyelocytic leukemia HL-60 cell line. Treatment of HL-60 cells with an antisense oligodeoxyribonucleotide complementary to the start codon and the next four codons of c-myc mRNA has previously been observed to inhibit c-myc protein expression and cell proliferation in a sequence-specific, dose-dependent manner. Comparable effects are seen upon treatment of HL-60 cells with dimethylsulfoxide (Me2SO), which is also know to induce granulocytic differentiation of HL-60 cells. Hence, the effects of antisense oligomers on cellular differentiation were examine and compared with Me2SO. Differentiation of HL-60 cells into forms with granulocytic characteristics was found to be enhanced in a sequence-specific manner by the anti-c-myc oligomer. No synergism was observed between the anti-c-myc oligomer and Me2SO in stimulating cellular differentiation. In contrast, synergism did appear in the inhibition of cell proliferation. Finally, the anti-c-myc oligomer uniformly inhibited colony formation in semisolid medium. It is possible that further reduction in the level of c-myc expression by antisense oligomer inhibition may be sufficient to allow terminal granulocytic differentiation and reverse transformation.

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Author notes

  1. Erica L. Wickstrom

    Present address: Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 02139, Cambridge, MA

Authors and Affiliations

  1. Department of Chemistry, University of South Florida, 33620, Tampa, Florida

    Erica L. Wickstrom, Thomas A. Bacon, Audrey Gonzalez & Eric Wikstrom

  2. Department of Internal Medicine, University of South Florida, 33620, Tampa, Florida

    Gary H. Lyman

  3. Department of Biochemistry and Molecular Biology, University of South Florida, 33620, Tampa, Florida

    Eric Wikstrom

Authors
  1. Erica L. Wickstrom
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  2. Thomas A. Bacon
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  3. Audrey Gonzalez
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  4. Gary H. Lyman
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  5. Eric Wikstrom
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Additional information

This work was supported by grants to E. W. from the National Institutes of Health, Bethesda, MD (CA 42960), and the Leukemia Society of America.

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Wickstrom, E.L., Bacon, T.A., Gonzalez, A. et al. Anti-c-myc DNA increases differentiation and decreases colony formation by HL-60 cells. In Vitro Cell Dev Biol 25, 297–302 (1989). https://doi.org/10.1007/BF02628470

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  • DOI: https://doi.org/10.1007/BF02628470

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