Anti-c-myc DNA increases differentiation and decreases colony formation by HL-60 cells.
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.
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- Tumor Cells, Cultured
- Tetradecanoylphorbol Acetate
- Proto-Oncogene Proteins c-myc
- Proto-Oncogene Proteins
- Proto-Oncogene Mas
- Oxidation-Reduction
- Oligonucleotides, Antisense
- Oligonucleotides
- Nitroblue Tetrazolium
- Leukemia, Promyelocytic, Acute
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Tetradecanoylphorbol Acetate
- Proto-Oncogene Proteins c-myc
- Proto-Oncogene Proteins
- Proto-Oncogene Mas
- Oxidation-Reduction
- Oligonucleotides, Antisense
- Oligonucleotides
- Nitroblue Tetrazolium
- Leukemia, Promyelocytic, Acute