Abstract
The cellular levels of topoisomerase II expression were compared between 10 fresh human tumors and normal tissues to predict the selective anticancer effect of its inhibitors such as adriamycin and VP-16. Topoisomerase II expression was observed in 9 of the 10 tumor tissues (90.0 per cent), 3 of which showed extremely high levels, whereas only 5 of the normal tissues (50.0 per cent) expressed any cellular topoisomerase II and the levels were not higher than those seen in the cancer cells. Six of the 9 positive tumors showed a higher level of topoisomerase II expression than the normal tissues, while the other 3 showed the same level. It can be interpreted from these results that topoisomerase II inhibitors could be effective in cancer patients due to the greater level of this enzyme in tumor cells than in normal tissues. Thus, it is suggested that a comparative analysis of topoisomerase II expression between tumors and normal tissues may be useful for predicting the selective cytotoxicity of topoisomerase II inhibitors in clinical practice.
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References
Lock RB, Ross WE. DNA topoisomerases in cancer therapy. Anti Cancer Drug Design 1987; 2: 151–164.
Drlica K, Franco RJ. Inhibitors of DNA topoisomerases. Biochemistry 1988; 27: 2253–2259.
Liu LF. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 1989; 58: 351–357.
Hsiang Y-H, Hertzberg R, Hecht S, Liu LF. Camptothecin induced protein-linked DNA breaksvia mammalian DNA topoisomerase I. J Biol Chem 1985; 260: 14873–14878.
Tewey KM, Chen GL, Nelson EM, Liu LF. Intercalative antitumor drugs interfere with the breakageunion reaction of mammalian DNA topoisomerase II. J Biol Chem 1984: 259: 9182–9187.
Sullivan DM, Glisson BS, Hodges PK, Smallwood-Kentro S, Ross WE. Proliferation dependence of topoisomerase II-mediated drug action. Biochemistry 1986; 25: 2248–2256.
Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: a laboratory mannual. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. 1982.
Thomas PS, Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci 1980; 77: 5201–5205.
Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci 1988: 85: 7177–7181.
Feiberg AP, Vogelstein B. A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 1983; 132: 6–13.
Hsiang Y-H, Wu H-Y, Liu LF. Proliferation-dependent regulation of DNA topoisomerase II in cultured human cells. Cancer Res 1988; 48: 3230–3235.
Hsiang Y-H, Wu H-Y, Liu LF. Topoisomerase: novel therapeutic targets in cancer chemotherapy. Biochem Parmacol 1988; 17: 1801–1802.
Heck MMS, Hittelman WN, Earnshaw WC. Differential expression of DNA topoisomerase I and II during the eukaryotic cell cycle. Proc Natl Acad Sci 1988; 85: 1086–1090.
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Kim, R., Hirabayashi, N., Nishiyama, M. et al. mRNA expression of topoisomerase II in human tumors and normal tissues. The Japanese Journal of Surgery 21, 587–589 (1991). https://doi.org/10.1007/BF02471001
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DOI: https://doi.org/10.1007/BF02471001