Abstract
DNA excision repair plays a significant part in platinum-based chemotherapy by removing DNA lesions caused by platinum-containing drugs. The nucleotide excision repair (NER) pathway is the mammalian DNA repair mechanism that removes bulky DNA adducts induced by DNA damaging chemotherapeutic agents. Platinum compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a platinum-DNA-adduct. The NER pathway is the main mechanism responsible for platinum resistance by increased platinum-DNA-adduct removal and the excision repair cross complementing-group 1 (ERCC1) gene plays a major role in the NER-pathway because of its damage recognition and excision ability. This chapter will review mechanisms of DNA repair and platinum resistance as it relates to the NER pathway and regulation of ERCC1. A brief discussion on the role of cancer stem cells in platinum resistance is also presented.
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References
Reed E (1998) Platinum-DNA adduct, nucleotide excision repair, and platinum based anti-cancer chemotherapy. Cancer Treat Rev 24:331–344
Reed E (1998) Nucleotide excision repair and anti-cancer chemotherapy. Cytotechnology 27:187–201
Reed E (2008) Cisplatin and platinum analogs. In: DeVita VT, Rosenberg SA, Lawrence TS (eds) Cancer principles and practice of oncology, 8th edn. Lippincott, Williams, and Wilkins, Philadelphia, pp 419–26
Reed E (2006) Cisplatin, carboplatin, and oxaliplatin. In: Chabner BA, Longo DL (eds) Cancer chemotherapy and biotherapy: principles and practice, 4th edn. Lippincott, Williams & Wilkins, Philadelphia, pp 332–343
Westerveld A, Hoeijmakers JH, van Duin M, de Wit J, Odijk H, Pastink A, Wood RD, Bootsma D (1984) Molecular cloning of a human DNA repair gene. Nature 310:425–429
Weeda G, Donker I, de Wit J, Morreau H, Janssens R, Vissers CJ, Nigg A, van Steeg H, Bootsma D, Hoeijmakers JH (1997) Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr Biol 7:427–439
Xu H, Swoboda I, Bhalla PL et al (1998) Plant homologue of human excision repair gene ERCC1 points to conversation of DNA repair mechanisms. Plant J 13:823–829
Lin J-J, Sancar A (1992) Active site of (A)BC excinuclease: I. Evidence for 5’ incision by UvrC through a catalytic site involving Asp399, Asp438, Asp466, and His538 residues. J Biol Chem 267:17688–17692
Verhoeven EEA, van Kesteren M, Moolenaar GF, Visse R, Goosen N (2000) Catalytic sites for 3’ and 5’ incision of Escherichia coli nucleotide excision repair are both located in UvrC. J Biol Chem 275:5120–5123
Lee KB, Parker RJ, Bohr VA, Cornelison TC, Reed E (1993) Cisplatin sensitivity/resistance in UV-repair deficient Chinese hamster ovary cells of complementation groups 1 and 3. Carcinogenesis 14:2177–2180
Reed E, Sauerhoff S, Poirier MC (1988) Quantitation of platinum-DNA binding in human tissues following therapeutic levels of drug exposure – a novel use of graphite furnace spectrometry. Atom Spectrosc 9:93–95
Parker RJ, Eastman A, Bostick-Bruton F, Reed E (1991) Acquired cisplatin resistance in human ovarian cancer cells is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation. J Clin Invest 87:772–777
Parker RJ, Gill I, Tarone R, Vionnet J, Grunberg S, Muggia F, Reed E (1991) Platinum-DNA damage in leukocyte DNA of patients receiving carboplatin and cisplatin chemotherapy, measured by atomic absorption spectrometry. Carcinogenesis 12:1253–1258
Darcy KM, Tian C, Reed E (2007) Platinum-DNA adducts and ERCC1 expression in optimal, stage III epithelial ovarian cancer treated with platinum-taxane chemotherapy: a Gynecologic Oncology Group study. Cancer Res 67:4474–4481
Ahmad A, Robinson AR, Duensing A, van Drunen E, Beverloo HB, Weisberg DB, Hasty P, Hoeijmakers JH, Niedernhofer LJ (2008) ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol Cell Biol 28:5082–5092
Niedernhofer LJ, Odijk H, Budzowska M et al (2004) The structure-specific endonuclease ERCC1-XPF is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol 24:5776–5787
Ciccia A, McDonald N, West SC (2008) Structural and functional relationships of the XPF/MUS81 family of proteins. Annu Rev Biochem 77:259–287
Al-Minawi AZ, Lee YF, Hakansson D, Johansson F, Lundin C, Sleh-Gohari N, Schultz N, Jenssen D, Bryant HE, Meuth M, Hinz JM, Helleday T (2009) The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links. Nucleic Acids Res 27:6400–13
Wataru S, Swisher EM, Karlan BY et al (2008) Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 451:1116–1121
Livingston DM, Silver DP (2008) Cancer: crossing over to drug resistance. Nature 451:1066–1067
Swisher EM, Sakai W, Karlan BY, Wurz K, Urban N, Taniguichi T (2008) Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res 68:2581–2586
Wachters FM, Wong LS, Timens W, Kampinga HH, Groen HJ (2005) ERCC1, hRad51, and BRCA1 protein expression in relation to tumour response and survival of stage III/IV NSCLC patients treated with chemotherapy. Lung Cancer 50:211–219
Zwelling LA, Kohn KW, Ross WE, Ewig RAG, Anderson T (1978) Kinetics of formation and disappearance of a DNA cross-linking effect in mouse leukemia L1210 cells treated with cis- and trans-diammine-dichloroplatinum(II). Cancer Res 38:1762–1768
Ducore JM, Erickson LC, Zwelling LA, Laurent G, Kohn KW (1982) Comparative studies of DNA cross-linking and cytotoxicity in Burkitt’s lymphoma cell lines treated with cis-diamminedichloroplatinum(II) and L-phenylalanine mustard. Cancer Res 42:897–902
Dabholkar M, Bostick-Bruton F, Weber C, Bohr VA, Egwuagu C, Reed E (1992) ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients. J Natl Cancer Inst 84:1512–1517
Li Q, Gardner K, Zhang L, Tsang B, Bostick-Bruton F, Reed E (1998) Cisplatin induction of ERCC1 mRNA expression in A2780/CP70 human ovarian cancer cells. J Biol Chem 273:23419–23425
Li Q, Ding L, Yu JJ, Mu C, Tsang B, Bostick-Bruton F, Reed E (1998) Cisplatin and phorbol ester independently induce ERCC1 protein in human ovarian tumor cells. Int J Oncol 13:987–992
Li Q, Tsang B, Gardner K, Bostick-Bruton F, Reed E (1999) Phorbol ester exposure activates an AP-1 associated increase in ERCC1 mRNA expression in human ovarian cancer cells. Cell Mol Life Sci 55:456–466
Altaha R, Liang X, Yu JJ, Reed E (2004) ERCC-1 gene expression and platinum resistance. Int J Mol Med 14:959–970
Reed E (2006) ERCCI measurements in clinical oncology. New Engl J Med 355:1054–1055
Reed E (2005) ERCC1 and clinical resistance to platinum-based therapy. Clin Cancer Res 11:6100–6102
Bonovich M, Olive M, Reed E, O’Connell B, Vinson C (2002) Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines. Cancer Gene Ther 9:62–70
Li Q, Bostick-Bruton F, Reed E (1999) Modulation of ERCC-1 mRNA expression by pharmacological agents in human ovarian cancer cells. Biochem Pharmacol 57:347–353
Li Q, Bostick-Bruton F, Reed E (1998) Effect of interleukin-1 and tumor necrosis factor on cisplatin-induced ERCC1 mRNA expression in a human ovarian carcinoma cell line. Anticancer Res 18:2283–2287
Mimnaugh EG, Yunmbam MK, Li Q, Bonvini P, Hwang S-G, Trepel J, Reed E, Neckers L (2000) Proteasome inhibitors prevent cisplatin-DNA adduct repair and potentiate cisplatin-induced apoptosis in ovarian carcinoma cells. Biochem Pharmacol 60:1343–1354
Li QQ, Ding L, Reed E (2000) Proteasome inhibition suppresses cisplatin-dependent ERCC-1 mRNA expression in human ovarian tumor cells. Res Commun Mol Pathol Pharmacol 107:387–396
Zhong X, Li Q, Reed E (2003) SU5416 sensitizes ovarian cancer cells to cisplatin through inhibition of nucleotide excision repair. Cell Mol Life Sci 60:794–802
Parker RJ, Dabholkar M, Lee KB, Bostick-Bruton F, Reed E (1993) Taxol effect on cisplatin sensitivity and cisplatin cellular accumulation in human ovarian cancer cells. Monog Natl Cancer Inst 15:83–88
Benchekroun MN, Parker R, Reed E, Sinha BK (1993) Inhibition of DNA repair and sensitization of cisplatin in human ovarian cancer cells by interleukin-1-alpha. Biochem Biophys Res Comm 195:294–300
Benchekroun MN, Parker R, Dabholkar M, Reed E, Sinha BK (1995) Effects of interleukin-1-alpha on DNA repair on human ovarian carcinoma (NIH:OVARCAR-3) cells: implications in the mechanism of sensitization of cis-diamminedichloroplatinum (II). Mol Pharmacol 47:1255–1260
Lee KB, Parker RJ, Reed E (1995) Effect of cadmium on human ovarian cancer cells with acquired cisplatin resistance. Cancer Lett 88:57–66
Wang Z, Lee KB, Reed E, Sinha B (1996) Sensitization by interleukin-1α of carboplatinum antitumor activity against human ovarian (NIH:OVCAR-3) carcinoma cells in vitro and in vivo. Int J Cancer 67:583–587
Buell JR, Reed E, Lee KB, Parker RJ, Venson DJ, Amikura K, Arnold S, Fraker DL, Alexander HR (1997) Synergistic effect and molecular basis of tumor necrosis factor and cisplatin cytotoxicity and hyperthermia against gastric cancer cells. Ann Surg Oncol 4:141–148
Abernathy TV, Lee KB, Parker RJ, Reed E (1999) The measurement of cadmium in biological materials, using graphite furnace atomic absorption spectrometry with Zeeman background correction. Oncol Rep 6:155–159
Senderowicz A, Reid R, Headlee D, Abernathy T, Horti J, Lush RM, Reed E, Figg WD, Sausville EA (1999) A phase II trial of gallium nitrate in patients with androgen-independent metastatic prostate cancer. Urologia Internationalis 63:120–125
Yunmbam MK, Li QQ, Mimnaugh EG, Kayastha GL, Yu JJ, Jones LN, Neckers L, Reed E (2001) Effect of the proteasome inhibitor ALLnL on cisplatin sensitivity in human ovarian tumor cells. Int J Oncol 4:741–748
Li Q, Yunmbam MK, Zhong X, Yu JJ, Mimnaugh EG, Neckers L, Reed E (2001) Lactacystin enhances cisplatin sensitivity in resistant human ovarian cancer cell lines via inhibition of DNA repair and ERCC-1 expression. Cell Mol Biol (Noisy-le-grand) 47:OL61–OL72
Zhong X, Li X, Wang G, Zhu Y, Gu G, Zhao J, Neace C, Ding H, Reed E, Li QQ (2004) Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells. Int J Oncol 25:445–451
Li Q, Yu JJ, Mu C, Slavsky D, Yunmbam M, Cross CL, Bostick-Bruton F, Reed E (2000) Association between the level of ERCC1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells. AntiCancer Res 20:645–652
Dabholkar M, Vionnet JA, Bostick-Bruton F, Yu JJ, Reed E (1994) mRNA Levels of XPAC and ERCC1 in ovarian tumor tissue correlates with response to platinum containing chemotherapy. J Clin Invest 94:703–708
Dabholkar M, Vionnet J, Parker RJ, Bostick-Bruton F, Dobbins A, Reed E (1995) Expression of an alternatively spliced ERCC1 mRNA species, is related to reduced DNA repair efficiency in human T lymphocytes. Oncol Rep 2:209–214
Yu JJ, Mu C, Dabholkar M, Bostick-Bruton F, Reed E (1998) Alternative splicing of ERCC1 and cisplatin-DNA adduct repair in human tumor cell lines. Int J Mol Med 1:617–620
Yu JJ, Thornton K, Guo Y, Kotz H, Reed E (2001) An ERCC1 splicing variant involving the 5’UTR of the mRNA may have a transcriptional modulatory function. Oncogene 20:7694–7698
Yu JJ, Mu C, Lee KB, Okamoto A, Reed EL, Bostick-Bruton F, Mitchell KC, Reed E (1997) A nucleotide polymorphism in ERCC1 gene in human ovarian cancer cell lines and tumor tissues. Mutation Res 382:13–20
Yu JJ, Lee KB, Mu C, Li Q, Abernathy TV, Bostick-Bruton F, Reed E (2000) Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene. Int J Oncol 16:555–560
Bicher A, Ault K, Kimmelman A, Gershenson D, Reed E, Liang B (1997) Loss of heterozygosity in human ovarian cancer on chromosome 19q. Gyn Oncol 66:36–40
Yu JJ, Bicher A, Bostick-Bruton F, Reed E (2000) Absence of evidence for allelic loss or allelic gain for ERCC1 and for XPD in human ovarian cancer cells and tissues. Cancer Lett 151:127–132
Liang BC, Ross DA, Reed E (1995) Genomic copy number changes of DNA repair genes ERCC1 and ERCC2 in human gliomas. J Neuro Oncol 26:17–23
States JC, Reed E (1996) Enhanced XPA mRNA levels in cisplatin-resistant human ovarian cancer are not associated with XPA mutations or gene amplification. Cancer Lett 108:233–237
Hromas R, Davis B, Rauscher FJ et al (1996) Hematopoietic transcriptional regulation by the myeloid zinc finger gene, MZF-1. Curr Top Microbiol Immunol 211:159–164
Peterson MJ, Morris JF (2000) Human myeloid zinc finger gene MZF produces multiple transcripts and encodes a SCAN box protein. Gene 254:105–118
Hoffman SMG, Hromas R, Amemiya C, Mohrenweiser HW (1996) The location of MZF-1 at the telomere of human chromosome 19q makes it vulnerable to degeneration in aging cells. Leukemia Res 20:281–283
Zhong Z, Thornton K, Reed E (2000) Computer based analyses of the 5’-flanking regions of selected genes involved in the nucleotide excision repair excision complex. Int J Oncol 17:375–380
Yan QW, Reed E, Zhong XS, Thornton K, Guo Y, Yu JJ (2006) MZF1 possesses arepressively regulatory function in ERCC1 expression. Biochem Pharmacol 71:761–771
Dabholkar M, Bostick-Bruton F, Weber C, Egwuagu C, Bohr VA, Reed E (1993) Expression of excision repair genes in non-malignant bone marrow from cancer patients. Mutation Res 293:151–160
Reed E, Dabholkar M, Thornton K, Thompson C, Yu JJ, Bostick-Bruton F (2000) Evidence for “order” in the appearance of mRNAs of nucleotide excision repair genes, in human ovarian cancer tissues. Oncol Rep 7:1123–1128
Dabholkar M, Thornton K, Vionnet J, Bostick-Bruton F, Yu JJ, Reed E (2000) Increased mRNA levels of XPB and CSB without increased mRNA levels of MDR1 or MT-II in platinum-resistant human ovarian cancer tissues. Biochem Pharmacol 60:1611–1619
Reed E, Yu JJ, Davies A, Gannon J, Armentrout SL (2003) Clear cell tumors have higher mRNA levels of ERCC1 and XPB than other histological types of epithelial ovarian cancer. Clin Cancer Res 9:5299–5305
Dabholkar MD, Berger MS, Vionnet JA, Egwuagu C, Silber JR, Yu JJ, Reed E (1995) Malignant and non-malignant brain tissues differ in their mRNA expression patterns for ERCC1 and ERCC2. Cancer Res 55:1261–1266
Dabholkar MD, Berger MS, Vionnet JA, Overton L, Bostick-Bruton F, Yu JJ, Silber JR, Reed E (1996) Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain. Mol Carcinogenesis 17:1–7
Zhang S, Balch C, Chan MW et al (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. ancer Res 68:4311–4320
Zietarska M, Maugard CM, Filali-Mouhim A et al (2007) Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer. Mol Carcinogenesis 46:872–885
Burleson KM, Casey RC, Skubitz KM et al (2004) Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol 93:170–181
Casey RC, Burleson KM, Skubitz KM et al (2001) Beta1-integrins regulate the formation and adhesion of ovarian carcinoma multicellular spheroids. Am J Pathol 159:2071–2080
Behrens BC, Hamilton TC, Masuda H, Grotzinger KR, Whang-Peng J, Louie KG, Knutsen T, McKoy WM, Young RC, Ozols RF (1987) Characterization of a cis-diamminedichloroplatinum(II)-resistant human ovarian cancer cell line and its use in evaluation of platinum analogues. Cancer Res 47:414–418
Bapat SA, Mali AM, Koppikar CB, Kurrey NK (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res Apr 15;65(8):3025–9
Gu G, Yuan J, Wills M, Kasper S (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res May 15;67(10):4807–15
Louie KG, Behrens BC, Kinsella TJ, Hamilton TC, Grotzinger KR, McKoy WM, Winker MA, Ozols RF (1885) Radiation survival parameters of antineoplastic drug-sensitive and –resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine. Cancer Res 45:2110–2115
Laner-Plamberger S, Kaser A, Paulischta M, Hauser-Kronberger C, Eichberger T, Frischauf AM (2009) Cooperation between Gli and Jun enhances transcription of Jun and selected Gli target genes. Oncogene 28:1639–1651
Zhen W, Link CL, O’Connor PM, Reed E, Parker R, Howell SB, Bohr VA (1992) Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin-resistant human ovarian cancer cell lines. Mol Cell Biol 12:3689–3698
Jones JC, Zhen WP, Reed E, Parker RJ, Sancar A, Bohr VA (1991) Gene-specific formation and repair of cisplatin intrastrand adducts and interstrand cross-links in Chinese hamster ovary cells. J Biol Chem 266:7101–7107
Eva A, Robbins K, Anderson P, Srinivasan A, Tronick S, Reddy E, Zilmore N, Gallen A, Laulenberger J, Papas T, Westin E, Wong-Staal F, Gallo R, and Aaronson S (1982) Cellular genes analogous to retroviral one genes are transcribed in 33. human tumor cells. Nature 295:116–119
Lai G, Ozols RF, Smyth JF, Young RC, and Hamilton TC (1988) Enhanced DNA repair and resistance to cisplatin in human ovarian cancer. Biochem. Pharmacol 37:4597–4600
Theunissen J-W, de Sauvage FJ (2009) Paracrine Hedgehog signaling in cancer. Cancer Res 69:6007–6010
Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN, Matsui W (2007) Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA 104:4048–4053
Kinzler KW, Vogelstein B (1990) The Gli gene encodes a nuclear protein which binds specific sequences in the human genome. Mol Cell Biol 10:634642
Tian H, Callahan CA, DuPree KJ, Darbonne WC, Ahn CP, Scales SJ, de Sauvage FJ (2009) Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci USA 106:4254–5259
Liao X, Siu MKY, Au Christy WH, Wong ESY, Chan HY, Ip PPC, Ngan HYS, Cheung ANY (2009) Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30:131–140
Bhattacharya R, Kwon J, Ali B, Wang E, Patra S, Shridhar V, Mukherjee P (2008) Role of hedgehog signaling in ovarian cancer. Clin Cancer Res 14:7659–7666
Chen X, Horiuchi A, Kikuchi N, Osada R, Yoshida J, Shiozawa T, Konishi I (2007) Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: it’s inhibition leads to growth suppression and apoptosis. Cancer Sci 98:68–76
Kudo K, Gavin E, Das S, Denny W, Jasmin M, Shevde-Samant L, Reed E (2010) Inhibition of Hedgehog results in altered regulation of c-jun and of ERCC1, in cisplatin-resistant A2780-CP70 human ovarian cancer cells [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17–21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 70(8 Suppl): LB–281
Reed E, Kudo K, Shevede-Samant L, Das S, Denny W, Gavin E, Jasmin M (2010) Factors that influence the regulation of ERCC1 in drug resistant cells [abstract]. In: Proceedings of the AACR International Conference on Translational Cancer Medicine; Mar 21–24, 2010; Amsterdam, The Netherlands: Clin Cancer Res16(7 Suppl): CN4–3
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Reed, E., Larkins, T.L., Chau, C.H., Figg, W.D. (2014). DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance. In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_18
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