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

Published

Journal Article

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 known to induce granulocytic differentiation of HL-60 cells. Hence, the effects of antisense oligomers on cellular differentiation were examined 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.

Full Text

Duke Authors

Cited Authors

  • Wickstrom, EL; Bacon, TA; Gonzalez, A; Lyman, GH; Wickstrom, E

Published Date

  • March 1989

Published In

Volume / Issue

  • 25 / 3 Pt 1

Start / End Page

  • 297 - 302

PubMed ID

  • 2647708

Pubmed Central ID

  • 2647708

International Standard Serial Number (ISSN)

  • 0883-8364

Language

  • eng

Conference Location

  • United States