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.
Wickstrom
E L
EL
Department of Chemistry, University of South Florida, Tampa 33620.
Bacon
T A
TA
Gonzalez
A
A
Lyman
G H
GH
Wickstrom
E
E
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004357:Drug Synergism; D006098:Granulocytes / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense; D010084:Oxidation-Reduction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D009580:Nitroblue Tetrazolium; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide