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Human Promyelocytic Leukemia HL-60 Cell Proliferation and c-myc Protein Expression are Inhibited by an Antisense Pentadecadeoxynucleotide Targeted against c-myc mRNA
Erica L. Wickstrom, Thomas A. Bacon, Audrey Gonzalez, Dennis L. Freeman, Gary H. Lyman and Eric Wickstrom
Proceedings of the National Academy of Sciences of the United States of America
Vol. 85, No. 4 (Feb. 15, 1988), pp. 1028-1032
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/30927
Page Count: 5
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The human promyelocytic leukemia cell line HL-60 overexpresses the c-myc protooncogene. A calculated secondary structure for c-myc mRNA placed the initiation codon in a bulge of a weakly base-paired region. Treatment of HL-60 cells with 5′ d(AACGTTGAGGGGCAT) 3′, complementary to the initiation codon and the next four codons of c-myc mRNA, inhibited c-myc protein expression in a dose-dependent manner. However, treatment of HL-60 cells with 5′ d(TTGGGATAACACTTA) 3′, complementary to nucleotides 17-31 of vesicular stomatitis virus matrix protein mRNA, displayed no such effects. These results agree with analogous studies of normal human T lymophocytes [Heikkila, R., Schwab, G., Wickstrom, E., Loke, S. L., Pluznik, D. H., Watt, R. & Neckers, L. M. (1987) Nature (London) 328, 445-449], except that only one-third as much oligomer was needed for a comparable effect. Proliferation of HL-60 cells in culture was inhibited in a sequence-specific, dose-dependent manner by the c-myc-complementary oligomer, but neither the oligomer complementary to vesicular stomatitis virus matrix protein mRNA nor 5′ d(CATTTCTTGCTCTCC) 3′, complementary to nucleotides 5399-5413 of human immunodeficiency virus tat gene mRNA, inhibited proliferation. It thus appears that antisense oligodeoxynucleotides added to myc-transformed cells via culture medium are capable of eliciting sequence-specific, dose-dependent inhibition of c-myc protein expression and cell proliferation.
Proceedings of the National Academy of Sciences of the United States of America © 1988 National Academy of Sciences