Abstract
Elucidation of the relationship between poly-ADP-ribosylation and carcinogenesis has markedly progressed by the recent development of knockout or transgenic mice models of poly(ADP-ribose) polymerase (Parp)-1, Parp-2, and poly(ADP-ribose) glycohydrolase (Parg). Parp-1 is involved in base excision repair (BER), single- and |double-strand break repair, and chromosomal stability. These multiple functions explain why Parp-1 deficiency enhances carcinogenesis induced by alkylating agents and that in aged animals. Parp-1 is also involved in transcriptional regulation through protein-protein interaction as a coactivator and/or poly-ADP-ribosylation reaction and is possibly involved in epigenetic alteration during carcinogenesis and modulation of tumor phenotypes. Parp-1-dependent cell-death accompanying NAD depletion may be another important issue in carcinogenesis because this process could lead to the selection of Parp-1 deficient cells due to their survival advantage during cancer growth. The relationship of Parp-2, Parp-3, tankyrase and Parg with carcinogenesis is also discussed.
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References
Armitage P, Doll R. The age distribution of cancer and a multi-stage theory of carcinogenesis. Br J Cancer 1954; 8(1):1–12.
Sugimura T. Multistep carcinogenesis: A 1992 perspective. Science 1992; 258(5082):603–607.
Masutani M, Nakagama H, Sugimura T. Poly(ADP-ribose) and carcinogenesis. Genes Chromosomes Cancer 2003; 38(4):339–348.
Masutani M, Suzuki H, Kamada N et al. Poly(ADP-ribose) polymerase gene disruption conferred mice resistant to streptozotocin-induced diabetes. Proc Natl Acad Sci USA 1999; 96(5):2301–2304.
Wang ZQ, Auer B, Stingl L et al. Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev 1995; 9(5):509–520.
de Murcia JM, Niedergang C, Trucco C et al. Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci USA 1997; 94(14):7303–7307.
Tong WM, Cortes U, Hande MP et al. Synergistic role of Ku80 and poly(ADP-ribose) polymerase in suppressing chromosomal aberrations and liver cancer formation. Cancer Res 2002; 62(23):6990–6996.
Tsutsumi M, Masutani M, Nozaki T et al. Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout mice to nitrosamine carcinogenicity. Carcinogenesis 2001; 22(1):1–3.
Nozaki T, Fujihara H, Watanabe M et al. Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane. Cancer Sci 2003; 94(6):497–500.
Ide F, Oda H, Nakatsuru Y et al. Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis. Carcinogenesis 2001; 22(4):567–572.
Morrison C, Smith GC, Stingl L et al. Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis. Nat Genet 1997; 17(4):479–482.
Donehower LA, Harvey M, Slagle BL et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992; 356(6366):215–221.
Tong WM, Hande MP, Lansdorp PM et al. DNA strand break-sensing molecule poly(ADP-ribose) polymerase cooperates with p53 in telomere function, chromosome stability, and tumor suppression. Mol Cell Biol 2001; 21(12):4046–4054.
Beneke R, Moroy T. Inhibition of poly(ADP-ribose) polymerase activity accelerates T-cell lymphomagenesis in p53 deficient mice. Oncogene 2001; 20(56):8136–8141.
Tong WM, Ohgaki H, Huang H et al. Null mutation of DNA strand break-binding molecule poly(ADP-ribose) polymerase causes medulloblastomas in p53(-/-) Mice. Am J Pathol 2003; 162(1):343–352.
Lee Y, McKinnon PJ. DNA ligase IV suppresses medulloblastoma formation. Cancer Res 2002; 62(22):6395–6399.
Conde C, Mark M, Oliver FJ et al. Loss of poly(ADP-ribose) polymerase-1 causes increased tumour latency in p53-deficient mice. EMBO J 2001; 20(13):3535–3543.
Kim PK, Zamora R, Petrosko P et al. The regulatory role of nitric oxide in apoptosis. Int Immunopharmacol 2001; 1(8):1421–1441.
Watanabe F, Masutani M, Kamada N et al. Impairment in S-phase entry of splenocytes of Parp-1 knockout mice. Proc Japan Acad 2003; 79 Ser B(8):248–251.
Schreiber V, Ame JC, Dolle P et al. Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J Biol Chem 2002; 277(25):23028–23036.
Augustin A, Spenlehauer C, Dumond H et al. PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression. J Cell Sci 2003; 116(Pt 8):1551–1562.
Smith S, Giriat I, Schmitt A et al. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 1998; 282(5393):1484–1487.
Gunji A, Fujihara H, Kamada N et al. Lack of altered frequency of sister-chromatid exchanges in poly(ADP-ribose) glycohydrolase-deficient mouse ES cells treated with methylmethanesulfonate. Proc Japan Acad 2003; 79 Ser B(10):305–307.
Hanai S, Kanai M, Ohashi S et al. Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in Drosophila melanogaster. Proc Natl Acad Sci USA 2004; 101(1):82–86.
Yamagami T, Miwa A, Takasawa S et al. Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors. Cancer Res 1985; 45(4):1845–1849.
Takahashi S, Ohnishi T, Denda A et al. Enhancing effect of 3-aminobenzamide on induction of gamma-glutamyl transpeptidase positive foci in rat liver. Chem Biol Interact 1982; 39(3):363–368.
Rosenberg MR, Novicki DL, Jirtle RL et al. Promoting effect of nicotinamide on the development of renal tubular cell tumors in rats initiated with diethylnitrosamine. Cancer Res 1985; 45(2):809–814.
Miwa M, Ishikawa T, Kondo T et al. Enhancement by 3-aminobenzamide of methylazoxymethanol acetate-induced hepatoma of the small fish “Medaka” (Oryzias latipes)”. In: Althaus FR, Hilz H, Shall S, eds. ADP-Ribosylation of Proteins. Berlin-Heidelberg-New York-Tokyo: Springer-Verag, 1985:480–483.
Miller EG, Rivera-Hidalgo F, Binnie WH. 3-Methoxybenzamide, a possible initiator for DMBA-induced carcinogenesis. In: Jacobson MK, Jacobson EL, eds. ADP-Ribose Transfer Reactions. Mechanisms and Biological Significance. New York: Springer-Verlag, 1989:287–290.
Rakieten N, Gordon BS, Beaty A et al. Pancreatic islet cell tumors produced by the combined action of streptozotocin and nicotinamide. Proc Soc Exp Biol Med 1971; 137(1):280–283.
Tsujiuchi T, Tsutsumi M, Denda A et al. Possible involvement of poly ADP-ribosylation in phenobarbital promotion of rat hepatocarcinogenesis. Carcinogenesis 1990; 11(10):1783–1787.
Nakagawa K, Utsunomiya J, Ishikawa T. Inhibition of methylazoxymethanol acetate initiation of colon carcinogenesis in rats by treatment with the poly(ADP-ribose)polymerase inhibitor 3-aminobenzamide. Carcinogenesis 1988; 9(7):1167–1171.
Denda A, Tsutsumi M, Yokose Y et al. Effects of 3-aminobenzamide on the induction of gamma-glutamyl-transpeptidase-positive foci by various chemicals in rat liver. Cancer Lett 1988; 39(1):29–36.
Boyonoski AC, Spronck JC, Gallacher LM et al. Niacin deficiency decreases bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. J Nutr 2002; 132(1):108–114.
Boyonoski AC, Spronck JC, Jacobs RM et al. Pharmacological intakes of niacin increase bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. J Nutr 2002; 132(1):115–120.
Kun E, Kirsten E, Milo GE et al. Cell cycle-dependent intervention by benzamide of carcinogen-induced neoplastic transformation and in vitro poly(ADP-ribosyl)ation of nuclear proteins in human fibroblasts. Proc Natl Acad Sci USA 1983; 80(23):7219–7223.
Borek C, Ong A, Morgan WF et al. Inhibition of X-ray-and ultraviolet light-induced transformation in vitro by modifiers of poly(ADP-ribose) synthesis. Radiat Res 1984; 99(2):219–227.
Borek C, Cleaver JE. Antagonistic action of a tumor promoter and a poly(adenosine diphosphoribose) synthesis inhibitor in radiation-induced transformation in vitro. Biochem Biophys Res Commun 1986; 134(3):1334–1341.
Borek C, Morgan WF, Ong A et al. Inhibition of malignant transformation in vitro by inhibitors of poly(ADP-ribose) synthesis. Proc Natl Acad Sci USA 1984; 81(1):243–247.
Lubet RA, McCarvill JT, Putman DL et al. Effect of 3-aminobenzamide on the induction of toxicity and transformation by ethyl methanesulfonate and methylcholanthrene in BALB/3T3 cells. Carcinogenesis 1984; 5(4):459–462.
Lubet RA, McCarvill JT, Schwartz JL et al. Effects of 3-aminobenzamide on the induction of morphologic transformation by diverse compounds in Balb/3T3 cells in vitro. Carcinogenesis 1986; 7(1):71–75.
Borek C, Ong A, Cleaver JE. Methylating and ethylating carcinogens have different requirements for poly(ADP-ribose) synthesis during malignant transformation. Carcinogenesis 1984; 5(12):1573–1576.
Strain AJ. Inhibitors of ADP-ribosyl transferase enhance the transformation of NIH3T3 cells following transfection with SV40 DNA. Exp Cell Res 1985; 159(2):531–535.
Ohashi Y, Ueda K, Hayaishi O et al. Induction of murine teratocarcinoma cell differentiation by suppression of poly(ADP-ribose) synthesis. Proc Natl Acad Sci USA 1984; 81(22):7132–7136.
Terada M, Fujiki H, Marks PA et al. Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds. Proc Natl Acad Sci USA 1979; 76(12):6411–6414.
Brac T, Ebisuzaki K. Inhibitors of poly(ADP-ribose) polymerase prevent Friend cell differentiation. In: Althaus FR, Hilz H, Shall S, eds. ADP-Ribosylation of Proteins. Berlin-Heidelberg-New York-Tokyo: Springer, 1985:446–452.
Nakayasu M, Shima H, Aonuma S et al. Deletion of transfected oncogenes from NIH 3T3 transformants by inhibitors of poly(ADP-ribose) polymerase. Proc Natl Acad Sci USA 1988; 85(23):9066–9070.
Shima H, Nakayasu M, Aonuma S et al. Loss of the MYC gene amplified in human HL-60 cells after treatment with inhibitors of poly(ADP-ribose) polymerase or with dimethyl sulfoxide. Proc Natl Acad Sci USA 1989; 86(19):7442–7445.
Bauer PI, Kirsten E, Varadi G et al. Reversion of malignant phenotype by 5-iodo-6-amino-1,2-benzopyrone a noncovalently binding ligand of poly(ADP-ribose) polymerase. Biochimie 1995; 77(5):374–377.
Nozaki T, Masutani M, Watanabe M et al. Syncytiotrophoblastic giant cells in teratocarcinoma-like tumors derived from Parp-disrupted mouse embryonic stem cells. Proc Natl Acad Sci USA 1999; 96(23):13345–13350.
Hemberger M, Nozaki T, Winterhager E et al. Parp1-deficiency induces differentiation of ES cells into trophoblast derivatives. Dev Biol 2003; 257(2):371–381.
Hans MA, Muller M, Meyer-Ficca M et al. Overexpression of dominant negative PARP interferes with tumor formation of HeLa cells in nude mice: Evidence for increased tumor cell apoptosis in vivo. Oncogene 1999; 18(50):7010–7015.
Caldecott KW. Protein-protein interactions during mammalian DNA single-strand break repair. Biochem Soc Trans 2003; 31 (Pt 1):247–251.
Divine KK, Gilliland FD, Crowell RE et al. The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Mutat Res 2001; 461(4):273–278.
El-Khamisy SF, Masutani M, Suzuki H et al. A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res 2003; 31(19):5526–5533.
Dantzer F, Schreiber V, Niedergang C et al. Involvement of poly(ADP-ribose) polymerase in base excision repair. Biochimie 1999; 81(1–2):69–75.
von Kobbe C, Harrigan JA, May A et al. Central role for the Werner syndrome protein/poly(ADP-ribose) polymerase 1 complex in the poly(ADP-ribosyl)ation pathway after DNA damage. Mol Cell Biol 2003; 23(23):8601–8613.
Opresko PL, Cheng WH, von Kobbe C et al. Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis 2003; 24(5):791–802.
Malagna M, Althaus FR. Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and induces DNA strand break resealing. J Biol Chem 2004; 279(7):5244–5248.
Ruscetti T, Lehnert BE, Halbrook J et al. Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase. J Biol Chem 1998; 273(23):14461–14467.
Ariumi Y, Masutani M, Copeland TD et al. Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro. Oncogene 1999; 18(32):4616–4625.
Brown ML, Franco D, Burkle A et al. Role of poly(ADP-ribosyl)ation in DNA-PKcs-independent V(D)J recombination. Proc Natl Acad Sci USA 2002; 99(7):4532–4537.
Adelfalk C, Kontou M, Hirsch-Kauffmann M et al. Physical and functional interaction of the Werner syndrome protein with poly-ADP ribosyl transferase. FEBS Lett 2003; 554(1–2):55–58.
Li B, Nacarro S, Kasahara N et al. Identification and biochemical characterization of a Werner syndrome protein complex with Ku70/80 and PARP-1. J Biol Chem 2004; 279(14):13659–13667.
Simbulan-Rosenthal CM, Haddad BR, Rosenthal DS et al. Chromosomal aberrations in PARP(-/-) mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc Natl Acad Sci USA 1999; 96(23):13191–13196.
Nozaki T, Fujihara H, Kamada N et al. Hyperploidy of embryonic fibroblasts derived from Parp-1 knockout mouse. Proc Japan Acad 2001; 77Ser B(6):121–124.
Simbulan-Rosenthal CM, Rosenthal DS, Luo R et al. Inhibition of poly(ADP-ribose) polymerase activity is insufficient to induce tetraploidy. Nucleic Acids Res 2001; 29(3):841–849.
Wang ZQ, Stingl L, Morrison C et al. PARP is important for genomic stability but dispensable in apoptosis. Genes Dev 1997; 11(18):2347–2358.
Vaziri H, West MD, Allsopp RC et al. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase. EMBO J 1997; 16(19):6018–6033.
Nozaki T, Masutani M, Akagawa T et al. Suppression of G1 arrest and enhancement of G2 arrest by inhibitors of poly(ADP-ribose) polymerase: Possible involvement of poly(ADP-ribosyl)ation in cell cycle arrest following gamma-irradiation. Jpn J Cancer Res 1994; 85(11):1094–1098.
Wieler S, Gagne JP, Vaziri H et al. Poly(ADP-ribose) polymerase-1 is a positive regulator of the p53-mediated G1 arrest response following ionizing radiation. J Biol Chem 2003; 278(21):18914–18921.
Agarwal ML, Agarwal A, Taylor WR et al. Defective induction but normal activation and function of p53 in mouse cells lacking poly-ADP-ribose polymerase. Oncogene 1997; 15(9):1035–1041.
Frouin I, Maga G, Denegri M et al. Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners. J Biol Chem 2003; 278(41):39265–39268.
Kanai M, Tong WM, Sugihara E et al. Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Mol Cell Biol 2003; 23(7):2451–2462.
Halappanavar SS, Shah GM. Defective control of mitotic and post-mitotic checkpoints in poly(ADP-ribose) polymerase-1(-/-)fibroblasts after mitotic spindle disruption. Cell cycle 2004; 3(3):335–342.
Sugimura T, Ushijima T. Genetic and epigenetic alterations in carcinogenesis. Mutat Res 2000; 462(2–3):235–246.
Gaudet F, Hodgson JG, Eden A et al. Induction of tumors in mice by genomic hypomethylation. Science 2003; 300(5618):489–492.
Zardo G, D’Erme M, Reale A et al. Does poly(ADP-ribosyl)ation regulate the DNA methylation pattern? Biochemistry 1997; 36(26):7937–7943.
de Capoa A, Febbo FR, Giovannelli F et al. Reduced levels of poly(ADP-ribosyl)ation result in chromatin compaction and hypermethylation as shown by cell-by-cell computer-assisted quantitative analysis. FASEB J 1999; 13(1):89–93.
Tulin A, Spradling A. Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science 2003; 299(5606):560–562.
Simbulan-Rosenthal CM, Ly DH, Rosenthal DS et al. Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase. Proc Natl Acad Sci USA 2000; 97(21):11274–11279.
Hassa PO, Hottiger MO. A role of poly(ADP-ribose) polymerase in NF-kappaB transcriptional activation. Biol Chem 1999; 380(7–8):953–959.
Ota K, Kameoka M, Tanaka Y et al. Expression of histone acetyltransferases was down-regulated in poly(ADP-ribose) polymerase-1-deficient murine cells. Biochem Biophys Res Commun 2003; 310(2):312–317.
Graeber TG, Osmanian C, Jacks T et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 1996; 379(6560):88–91.
Yu SW, Wang H, Poitras MF et al. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 2002; 297(5579):259–263.
Eliasson MJ, Sampei K, Mandir AS et al. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 1997; 3(10):1089–1095.
Burkart V, Wang ZQ, Radons J et al. Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozotocin. Nat Med 1999; 5(3):314–319.
Pieper AA, Brat DJ, Krug DK et al. Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc Natl Acad Sci USA 1999; 96(6):3059–3064.
Bhatia KG, Cherney BW, Huppi K et al. A deletion linked to a poly(ADP-ribose) polymerase gene on chromosome 13q33-qter occurs frequently in the normal black population as well as in multiple tumor DNA. Cancer Res 1990; 50(17):5406–5413.
Bhatia K, Huppi K, Cherney B et al. Relative predispositional effect of a PADPRP marker allele in B-cell and some non B-cell malignancies. Curr Top Microbiol Immunol 1990; 166:347–357.
Lyn D, Cherney BW, Lalande M et al. A duplicated region is responsible for the poly(ADP-ribose) polymerase polymorphism, on chromosome 13, associated with a predisposition to cancer. Am J Hum Genet 1993; 52(1):124–134.
Prasad SC, Thraves PJ, Bhatia KG et al. Enhanced poly(adenosine diphosphate ribose) polymerase activity and gene expression in Ewing’s sarcoma cells. Cancer Res 1990; 50(1):38–43.
Soldatenkov VA, Albor A, Patel BK et al. Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor. Oncogene 1999; 18(27):3954–3962.
Bieche I, de Murcia G, Lidereau R. Poly(ADP-ribose) polymerase gene expression status and genomic instability in human breast cancer. Clin Cancer Res 1996; 2(7):1163–1167.
Rajaee-Behbahani N, Schmezer P, Ramroth H et al. Reduced poly(ADP-ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case-control study. Int J Cancer 2002; 98(5):780–784.
Masutani M, Nozaki T, Sasaki H et al. Aberration of poly(ADP-ribose) polymerase-1 gene in human tumor cell lines: Its expression and structural alterations. Proc Japan Acad 2004; 80Ser B(2):114–118.
Moolgavkar SH, Luebeck EG. Multistage carcinogenesis and the incidence of human cancer. Genes Chromosomes Cancer 2003; 38(4):302–306.
Bassing CH, Suh H, Ferguson DO et al. Histone H2AX: A dosage-dependent suppressor of oncogenic translocations and tumors. Cell 2003; 114(3):359–370.
Celeste A, Difilippantonio S, Difilippantonio MJ et al. H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 2003; 114(3):371–383.
Dumon-Jones V, Frappart PO, Tong WM et al. Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res 2003; 63(21):7263–7269.
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Masutani, M. et al. (2006). Role of Poly-ADP-Ribosylation in Cancer Development. In: Poly(ADP-Ribosyl)ation. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-36005-0_17
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