Molecular cloning of the genes suppressed in RVC lymphoma cells by topoisomerase inhibitors.
Etoposide is a topoisomerase II inhibitor that induces DNA cleavable complex and has been used as an antitumor drug. We isolated two genes that were transcriptionally suppressed at an early stage of incubation in etoposide-treated RVC lymphoma cells, using modified PCR-based subtractive hybridization. Sequencing revealed that one of these genes, which was approximately 1.7 kb and which encoded a protein of 320 amino acids, was identical to hnRNP A1. The other was a novel gene of about 2.2 kb encoding a protein of 469 amino acids. These genes were also down-regulated in the cells incubated with camptothecin, a topoisomerase I inhibitor that induces DNA single strand breaks, but not in those exposed to ICRF-154, a topoisomerase II inhibitor that does not induce DNA cleavable complex formation. These results suggest that the early down-regulation of these genes contributes to the cytotoxicity of the topoisomerase inhibitors that induce DNA cleavage.
Department of Biochemistry, Tokyo Dental College, Chiba, Japan.
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Onishi
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Kizaki
D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D008223:Lymphoma / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D016721:Radiation Leukemia Virus; D012261:Ribonucleoproteins / Q000235:genetics; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; D012261:Ribonucleoproteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D002166:Camptothecin