Three missense mutations of DNA topoisomerase I in highly camptothecin-resistant colon cancer cell sublines

Arakawa,Yasuhiro; Ozaki,Koji; Okawa,Yutaka; Yamada,Hisashi

doi:10.3892/or.2013.2594

Three missense mutations of DNA topoisomerase I in highly camptothecin-resistant colon cancer cell sublines

Authors:
- Yasuhiro Arakawa
- Koji Ozaki
- Yutaka Okawa
- Hisashi Yamada
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Affiliations: Department of Oncology and Hematology, Jikei University School of Medicine, Minato‑Ku, Tokyo 105‑8471, Japan, Department of Molecular Genetics, Jikei University School of Medicine, Minato‑Ku, Tokyo 105‑8471, Japan, Department of Internal Medicine, Sasaki Hospital, Fukaya, Saitama 366-0824, Japan
Published online on: July 5, 2013 https://doi.org/10.3892/or.2013.2594
Pages: 1053-1058
Copyright: © Arakawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Various anticancer drugs, including camptothecins and indolocarbazoles, target DNA topoisomerase I (Top1). We previously described the camptothecin-resistant colon cancer cell line DLDSNR6, which has a Gly365Ser missense mutation in Top1. In the present study, we established highly camptothecin-resistant sublines from DLDSNR6 cells by continuous exposure to higher camptothecin concentrations. The established sublines grew in the presence of 30 µM of camptothecin, but exhibited markedly retarded growth. In addition to Gly365Ser, these sublines harbored a Top1 Gly717Arg mutation and some had also a Top1 Gln421Arg mutation. Top1 activity was reduced to approximately one-eighth in highly resistant cell lines compared with that in parental DLD-1 cells. Resistant clones with 3 Top1 mutations including Gln421RArg exhibited the highest resistance to the indolocarbazole J-107088 in terms of the effect on the cell cycle distribution. The Gln421 mutation was equivalent to a mutation recently found in camptothecin biosynthesizing plants, but it has not previously been found in mammalian cells.

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1	Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB and Stewart L: The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci USA. 99:15387–15392. 2002. View Article : Google Scholar : PubMed/NCBI
2	Pommier Y and Cushman M: The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives. Mol Cancer Ther. 8:1008–1014. 2009. View Article : Google Scholar : PubMed/NCBI
3	Sáchez C, Médez C and Salas JA: Indolocarbazole natural products: occurrence, biosynthesis, and biological activity. Nat Prod Rep. 23:1007–1045. 2006.PubMed/NCBI
4	Wang JC: Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol. 3:430–440. 2002. View Article : Google Scholar : PubMed/NCBI
5	Marchand C, Antony S, Kohn KW, et al: A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex. Mol Cancer Ther. 5:287–295. 2006. View Article : Google Scholar
6	Urasaki Y, Laco G, Takebayashi Y, Bailly C, Kohlhagen G and Pommier Y: Use of camptothecin-resistant mammalian cell lines to evaluate the role of topoisomerase I in the antiproliferative activity of the indolocarbazole, NB-506, and its topoisomerase I binding site. Cancer Res. 61:504–508. 2001.PubMed/NCBI
7	Arakawa Y, Suzuki H, Saito S and Yamada H: Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cells. Mol Cancer Ther. 5:502–508. 2006. View Article : Google Scholar : PubMed/NCBI
8	Sirikantaramas S, Yamazaki M and Saito K: Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants. Proc Natl Acad Sci USA. 105:6782–6786. 2008. View Article : Google Scholar : PubMed/NCBI
9	Rasheed ZA and Rubin EH: Mechanisms of resistance to topoisomerase I-targeting drugs. Oncogene. 22:7296–7304. 2003. View Article : Google Scholar : PubMed/NCBI
10	Urasaki Y, Laco GS, Pourquier P, et al: Characterization of a novel topoisomerase I mutation from a camptothecin-resistant human prostate cancer cell line. Cancer Res. 61:1964–1969. 2001.PubMed/NCBI
11	Bonven BJ, Gocke E and Westergaard O: A high affinity topoisomerase I binding sequence is clustered at DNAase I hypersensitive sites in Tetrahymena R-chromatin. Cell. 41:541–551. 1985. View Article : Google Scholar : PubMed/NCBI
12	Chen TR, Dorotinsky CS, McGuire LJ, Macy ML and Hay RJ: DLD-1 and HCT-15 cell lines derived separately from colorectal carcinomas have totally different chromosome changes but the same genetic origin. Cancer Genet Cytogenet. 81:103–108. 1995. View Article : Google Scholar : PubMed/NCBI
13	Moisan F, Longy M, Robert J and Le Morvan V: Identification of gene polymorphisms of human DNA topoisomerase I in the National Cancer Institute panel of human tumour cell lines. Br J Cancer. 95:906–913. 2006. View Article : Google Scholar : PubMed/NCBI
14	Toyoda E, Kurosawa A, Fujii M and Adachi N: Heterozygous disruption of the DNA topoisomerase I gene confers cellular resistance to camptothecin in human cells. Biol Pharm Bull. 32:724–727. 2009. View Article : Google Scholar : PubMed/NCBI
15	Miao ZH, Player A, Shankavaram U, et al: Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analyses. Cancer Res. 67:8752–8761. 2007. View Article : Google Scholar : PubMed/NCBI
16	McClendon AK, Rodriguez AC and Osheroff N: Human topoisomerase IIα rapidly relaxes positively supercoiled DNA: implications for enzyme action ahead of replication forks. J Biol Chem. 280:39337–39345. 2005.
17	Redinbo MR, Stewart L, Kuhn P, Champoux JJ and Hol WG: Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science. 279:1504–1513. 1998. View Article : Google Scholar : PubMed/NCBI
18	Stewart L, Redinbo MR, Qiu X, Hol WG and Champoux JJ: A model for the mechanism of human topoisomerase I. Science. 279:1534–1541. 1998. View Article : Google Scholar : PubMed/NCBI
19	Chrencik JE, Staker BL, Burgin AB, et al: Mechanisms of camptothecin resistance by human topoisomerase I mutations. J Mol Biol. 339:773–784. 2004. View Article : Google Scholar : PubMed/NCBI
20	Laco GS, Collins JR, Luke BT, et al: Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model. Biochemistry. 41:1428–1435. 2002. View Article : Google Scholar : PubMed/NCBI
21	Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S and Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 234:81–89. 2006. View Article : Google Scholar : PubMed/NCBI
22	Komatani H, Kotani H, Hara Y, et al: Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 61:2827–2832. 2001.
23	Pommier Y: Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer. 6:789–802. 2006. View Article : Google Scholar : PubMed/NCBI
24	Wang LF, Ting CY, Lo CK, et al: Identification of mutations at DNA topoisomerase I responsible for camptothecin resistance. Cancer Res. 57:1516–1522. 1997.PubMed/NCBI