Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA.
Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA.
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DOI：
10.1073/pnas.85.4.1028
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发表时间：
1988-02
影响因子：
11.1
通讯作者：
E. Wickstrom;T. Bacon;Audrey M. Gonzalez;Dennis L. Freeman;G. Lyman;E. Wickstrom
中科院分区：
文献类型：
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作者：
E. Wickstrom;T. Bacon;Audrey M. Gonzalez;Dennis L. Freeman;G. Lyman;E. Wickstrom
人早幼粒细胞白血病细胞系HL-60过表达c-myc原癌基因。计算的c-myc mRNA二级结构将起始密码子置于弱碱基配对区域的凸起处。5' d（AACGTTGAGGGGCAT）3'（与c-myc mRNA的起始密码子和随后的4个密码子互补）处理HL-60细胞，以剂量依赖方式抑制c-myc蛋白的表达。然而，用与水泡性口炎病毒基质蛋白mRNA的核苷酸17-31互补的5' d（TTGGGATAACACTTA）3'处理HL-60细胞，没有显示出这种作用。这些结果与正常人T淋巴细胞的类似研究一致[Heikkila，R.，Schwab，G.，Wickstrom，E.，Loke，S. L.，Pluznik，D. H、瓦特河& Neckers，L. M.（1987）Nature（伦敦）328，445-449]，不同之处在于对于相当的效果仅需要三分之一的寡聚物。c-myc互补寡聚体以序列特异性、剂量依赖性的方式抑制HL-60细胞的增殖，但与水疱性口炎病毒基质蛋白mRNA互补的寡聚体和与人类免疫缺陷病毒达特基因mRNA核苷酸5399-5413互补的5' d（CATTTCTTGCTCTCC）3'均不抑制增殖。因此，似乎反义寡脱氧核苷酸通过培养基添加到myc转化的细胞能够引起c-myc蛋白表达和细胞增殖的序列特异性，剂量依赖性抑制。
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 lymphocytes [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.