Abstract
The role of DNA topoisomerases (Topo) IIα and IIβ was investigated in various drug-resistant melanoma cells. Melanoma cells resistant to etoposide, exhibited an up to tenfold reduced Topo II activity corresponding to an increasing degree of drug resistance indicating that modulation of Topo II activity contribute to the drug-resistant phenotype. The reduction of Topo II activity was reflected by decreased nuclear amounts of both Topo II isoforms. © 2000 Cancer Research Campaign
Keywords: melanoma, drug resistance, etoposide, cisplatin, fotemustine, vindesine
Full Text
The Full Text of this article is available as a PDF (122.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boege F., Andersen A., Jensen S., Zeidler R., Kreipe H. Proliferation-associated nuclear antigen Ki-S1 is identical with topoisomerase II alpha. Delineation of a carboxy-terminal epitope with peptide antibodies. Am J Pathol. 1995 Jun;146(6):1302–1308. [PMC free article] [PubMed] [Google Scholar]
- Campain J. A., Gottesman M. M., Pastan I. A novel mutant topoisomerase II alpha present in VP-16-resistant human melanoma cell lines has a deletion of alanine 429. Biochemistry. 1994 Sep 20;33(37):11327–11332. doi: 10.1021/bi00203a030. [DOI] [PubMed] [Google Scholar]
- Campain J. A., Padmanabhan R., Hwang J., Gottesman M. M., Pastan I. Characterization of an unusual mutant of human melanoma cells resistant to anticancer drugs that inhibit topoisomerase II. J Cell Physiol. 1993 May;155(2):414–425. doi: 10.1002/jcp.1041550224. [DOI] [PubMed] [Google Scholar]
- Danks M. K., Schmidt C. A., Cirtain M. C., Suttle D. P., Beck W. T. Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26. Biochemistry. 1988 Nov 29;27(24):8861–8869. doi: 10.1021/bi00424a026. [DOI] [PubMed] [Google Scholar]
- Danks M. K., Warmoth M. R., Friche E., Granzen B., Bugg B. Y., Harker W. G., Zwelling L. A., Futscher B. W., Suttle D. P., Beck W. T. Single-strand conformational polymorphism analysis of the M(r) 170,000 isozyme of DNA topoisomerase II in human tumor cells. Cancer Res. 1993 Mar 15;53(6):1373–1379. [PubMed] [Google Scholar]
- Jenkins J. R., Ayton P., Jones T., Davies S. L., Simmons D. L., Harris A. L., Sheer D., Hickson I. D. Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24. Nucleic Acids Res. 1992 Nov 11;20(21):5587–5592. doi: 10.1093/nar/20.21.5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellner U., Hutchinson L., Seidel A., Lage H., Danks M. K., Dietel M., Kaufmann S. H. Decreased drug accumulation in a mitoxantrone-resistant gastric carcinoma cell line in the absence of P-glycoprotein. Int J Cancer. 1997 May 29;71(5):817–824. doi: 10.1002/(sici)1097-0215(19970529)71:5<817::aid-ijc20>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
- Kern M. A., Helmbach H., Artuc M., Karmann D., Jurgovsky K., Schadendorf D. Human melanoma cell lines selected in vitro displaying various levels of drug resistance against cisplatin, fotemustine, vindesine or etoposide: modulation of proto-oncogene expression. Anticancer Res. 1997 Nov-Dec;17(6D):4359–4370. [PubMed] [Google Scholar]
- Lage H., Christmann M., Kern M. A., Dietel M., Pick M., Kaina B., Schadendorf D. Expression of DNA repair proteins hMSH2, hMSH6, hMLH1, O6-methylguanine-DNA methyltransferase and N-methylpurine-DNA glycosylase in melanoma cells with acquired drug resistance. Int J Cancer. 1999 Mar 1;80(5):744–750. doi: 10.1002/(sici)1097-0215(19990301)80:5<744::aid-ijc19>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
- Liu L. F. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 1989;58:351–375. doi: 10.1146/annurev.bi.58.070189.002031. [DOI] [PubMed] [Google Scholar]
- Liu L. F., Rowe T. C., Yang L., Tewey K. M., Chen G. L. Cleavage of DNA by mammalian DNA topoisomerase II. J Biol Chem. 1983 Dec 25;258(24):15365–15370. [PubMed] [Google Scholar]
- Marini J. C., Miller K. G., Englund P. T. Decatenation of kinetoplast DNA by topoisomerases. J Biol Chem. 1980 Jun 10;255(11):4976–4979. [PubMed] [Google Scholar]
- Nelson E. M., Tewey K. M., Liu L. F. Mechanism of antitumor drug action: poisoning of mammalian DNA topoisomerase II on DNA by 4'-(9-acridinylamino)-methanesulfon-m-anisidide. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1361–1365. doi: 10.1073/pnas.81.5.1361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Osheroff N., Corbett A. H., Robinson M. J. Mechanism of action of topoisomerase II-targeted antineoplastic drugs. Adv Pharmacol. 1994;29B:105–126. doi: 10.1016/s1054-3589(08)61134-5. [DOI] [PubMed] [Google Scholar]
- Son Y. S., Suh J. M., Ahn S. H., Kim J. C., Yi J. Y., Hur K. C., Hong W. S., Muller M. T., Chung I. K. Reduced activity of topoisomerase II in an Adriamycin-resistant human stomach-adenocarcinoma cell line. Cancer Chemother Pharmacol. 1998;41(5):353–360. doi: 10.1007/s002800050751. [DOI] [PubMed] [Google Scholar]
- Takano H., Kohno K., Ono M., Uchida Y., Kuwano M. Increased phosphorylation of DNA topoisomerase II in etoposide-resistant mutants of human cancer KB cells. Cancer Res. 1991 Aug 1;51(15):3951–3957. [PubMed] [Google Scholar]
- Walker P. R., Smith C., Youdale T., Leblanc J., Whitfield J. F., Sikorska M. Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes. Cancer Res. 1991 Feb 15;51(4):1078–1085. [PubMed] [Google Scholar]