Anticancer therapy targeting telomeres and telomerase: Current status

BioDrugs

Volumn 21, Issue 6, 2007, Pages 375-385

  Parkinson, E Kenneth ^a   Minty, Fay ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Cancer; Research and development; Telomerase inhibitors, general; Telomerase target

Indexed keywords

2 (3 NAPHTALEN 2 YLBUT 2 ENOYLAMINO)BENZOIC ACID; ANTINEOPLASTIC AGENT; ARSENIC; AS 1410; BENZOIC ACID DERIVATIVE; BIBR 1532; BRACO 19; CHAPERONE; FJ 5002; GEFITINIB; GRN 163; GRN 163L; HEAT SHOCK PROTEIN 90; INTERFERON; MST 312; NONSTEROID ANTIINFLAMMATORY AGENT; OLIGONUCLEOTIDE; PROTEIN P23; RAPAMYCIN; RETINOID; TANKYRASE; TELOMERASE; TELOMERASE INHIBITOR; TELOMESTATIN; UNCLASSIFIED DRUG; ZIDOVUDINE;

ANTINEOPLASTIC ACTIVITY; CANCER; CANCER THERAPY; CLINICAL TRIAL; DNA DAMAGE; DNA REPLICATION; DOWN REGULATION; DRUG MECHANISM; HUMAN; MAMMAL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SENESCENCE; TELOMERE;

EID: 36349005782     PISSN: 11738804     EISSN: None     Source Type: Journal    
DOI: 10.2165/00063030-200721060-00005     Document Type: Review

References (128)

1. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005 Sep 15; 19 (18): 2100-10
2. Watson JD. Origin of concatemeric T7 DNA. Nature: New Biol 1972 Oct 18; 239 (94): 197-201
3. Makarov VL, Hirose Y, Langmore JP. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 1997 Mar 7; 88 (5): 657-66
4. Lenain C, Bauwens S, Amiard S, et al. The Apollo 5′ exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol 2006 Jul 11; 16 (13): 1303-10
5. van Overbeek M, de Lange T. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr Biol 2006 Jul 11; 16 (13): 1295-302
6. Masutomi K, Yu EY, Khurts S, et al. Telomerase maintains telomere structure in normal human cells. Cell 2003 Jul 25; 114 (2): 241-53
7. Verdun RE, Crabbe L, Haggblom C, et al. Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell 2005 Nov 23; 20 (4): 551-61
8. Griffith JD, Comeau L, Rosenfield S, et al. Mammalian telomeres end in a large duplex loop. Cell 1999 May 14; 97 (4): 503-14
9. Stansel RM, de Lange T, Griffith JD. T-Loop assembly in vitro involves binding of TRF2 near the 3? telomeric overhang. EMBO J 2001 Oct 1; 20 (19): 5532-40
10. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994 Dec 23; 266 (5193): 2011-5
11. Nakamura TM, Morin GB, Chapman KB, et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997 Aug 15; 277 (5328): 955-9
12. Feng J, Funk WD, Wang SS, et al. The RNA component of human telomerase. Science 1995 Sep 1; 269 (5228): 1236-41
13. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature 1990 May 31; 345 (6274): 458-60
14. Hastie ND, Dempster M, Dunlop MG, et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 1990 Aug 30; 346 (6287): 866-8
15. Allsopp RC, Chang E, Kashefi-Aazam M, et al. Telomere shortening is associated with cell division in vitro and in vivo. Exp Cell Res 1995 Sep; 220 (1): 194-200
16. Munro J, Steeghs K, Morrison V, et al. Human fibroblast replicative senescence can occur in the absence of extensive cell division and short telomeres. Oncogene 2001 Jun 14; 20 (27): 3541-52
17. Frenck Jr RW, Blackburn EH, Shannon KM. The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci U S A 1998 May 12; 95 (10): 5607-10
18. Stewart SA, Ben-Porath I, Carey VJ, et al. Erosion of the telomeric single-strand overhang at replicative senescence. Nat Genet 2003 Apr; 33 (4): 492-6
19. Zhu XD, Niedernhofer L, Kuster B, et al. ERCC1/XPF removes the 3′ overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 2003 Dec; 12 (6): 1489-98
20. Chai W, Shay JW, Wright WE. Human telomeres maintain their overhang length at senescence. Mol Cell Biol 2005 Mar; 25 (6): 2158-68
21. d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003 Nov 13; 426 (6963): 194-8
22. Herbig U, Jobling WA, Chen BP, et al. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 2004 May 21; 14 (4): 501-13
23. Takai H, Smogorzewska A, de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003 Sep 2; 13 (17): 1549-56
24. Karlseder J, Broccoli D, Dai Y, et al. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 1999 Feb 26; 283 (5406): 1321-5
25. Webley K, Bond JA, Jones CJ, et al. Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Mol Cell Biol 2000 Apr; 20 (8): 2803-8
26. Stein GH, Dulic V. Origins of G1 arrest in senescent human fibroblasts. Bioessays 1995 Jun; 17 (6): 537-43
27. Eller MS, Liao X, Liu S, et al. A role for WRN in telomere-based DNA damage responses. Proc Natl Acad Sci U S A 2006 Oct 10; 103 (41): 15073-8
28. Rudolph KL, Millard M, Bosenberg MW, et al. Telomere dysfunction and evolution of intestinal carcinoma in mice and humans. Nat Genet 2001 Jun; 28 (2): 155-9
29. Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006 Nov 30; 444 (7119): 633-7
30. Bartkova J, Horejsi Z, Koed K, et al. DNA damage response as a candidate anticancer barrier in early human tumorigenesis. Nature 2005 Apr 14; 434 (7035): 864-70
31. Jacobs JJ, de Lange T. Significant role for p16INK4a in p53-independent telomere-directed senescence. Curr Biol 2004 Dec 29; 14 (24): 2302-8
32. Counter CM, Avilion AA, LeFeuvre CE, et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 1992 May; 11 (5): 1921-9
33. Artandi SE, DePinho RA. Mice without telomerase: what can they teach us about human cancer? Nat Med 2000 Aug; 6 (8): 852-5
34. Defendi V, Naimski P, Steinberg ML. Human cells transformed by SV40 revisited: the epithelial cells. J Cell Physiol 1982; 2: 131-40
35. Romanov SR, Kozakiewicz BK, Holst CR, et al. Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature 2001 Feb 1; 409 (6820): 633-7
36. Counter CM, Meyerson M, Eaton EN, et al. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene 1998 Mar 5; 16 (9): 1217-22
37. Bryan TM, Englezou A, Gupta J, et al. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 1995 Sep 1; 14 (17): 4240-8
38. Argilla D, Chin K, Singh M, et al. Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes. Cancer Cell 2004 Oct; 6 (4): 373-85
39. Bryan TM, Englezou A, Dalla-Pozza L, et al. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 1997 Nov; 3 (11): 1271-4
40. Hakin-Smith V, Jellinek DA, Levy D, et al. Alternative lengthening of telomeres and survival in patients with glioblastoma multiforme. Lancet 2003 Mar 8; 361 (9360): 836-8
41. Bednarek A, Budunova I, Slaga TJ, et al. Increased telomerase activity in mouse skin premalignant progression. Cancer Res 1995 Oct 15; 55 (20): 4566-9
42. Gonzalez-Suarez E, Samper E, Ramirez A, et al. Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J 2001 Jun 1; 20 (11): 2619-30
43. Stewart SA, Hahn WC, O'Connor BF, et al. Telomerase contributes to tumorigenesis by a telomere length-independent mechanism. Proc Natl Acad Sci U S A 2002 Oct 1; 99 (20): 12606-11
44. Chang S, Khoo CM, Naylor ML, et al. Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Genes Dev 2003 Jan 1; 17 (1): 88-100
45. Trapp S, Parcells MS, Kamil JP, et al. A virus-encoded telomerase RNA promotes malignant T cell lymphomagenesis. J Exp Med 2006 May 15; 203 (5): 1307-17
46. Geserick C, Tejera A, Gonzalez-Suarez E, et al. Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling. Oncogene 2006 Jul 20; 25 (31): 4310-9
47. Stampfer MR, Garbe J, Levine G, et al. Expression of the telomerase catalytic subunit, hTERT, induces resistance to transforming growth factor beta growth inhibition in p16INK4A(-) human mammary epithelial cells. Proc Natl Acad Sci U S A 2001 Apr 10; 98 (8): 4498-503
48. Lindvall C, Hou M, Komurasaki T, et al. Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene. Cancer Res 2003 Apr 15; 63 (8): 1743-7
49. Smith LL, Coller HA, Roberts JM. Telomerase modulates expression of growth-damage. controlling genes and enhances cell proliferation. Nature Cell Biol 2003 May; 5 (5): 474-9
50. Li S, Crothers J, Haqq CM, et al. Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA. J Biol Chem 2005 Jun 24; 280 (25): 23709-17
51. Soder AI, Hoare SF, Muir S, et al. Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer. Oncogene 1997 Mar 6; 14 (9): 1013-21
52. Zhang A, Zheng C, Lindvall C, et al. Frequent amplification of the telomerase reverse transcriptase gene in human tumors. Cancer Res 2000 Nov 15; 60 (22): 6230-5
53. Wu KJ, Grandori C, Amacker M, et al. Direct activation of TERT transcription by c-MYC. Nat Genet 1999 Feb; 21 (2): 220-4
54. Gewin L, Myers H, Kiyono T, et al. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16 E6/E6-AP complex. Genes Dev 2004 Sep 15; 18 (18): 2269-82
55. Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell 2003 Jun 27; 113 (7): 881-9
56. Rahman R, Latonen L, Wiman KG. hTERT antagonizes p53-induced apoptosis independently of telomerase activity. Oncogene 2005 Feb 17; 24 (8): 1320-7
57. Artandi SE, Chang S, Lee SL, et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 2000 Aug 10; 406 (6796): 641-5
58. Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998 Jan 16; 279 (5349): 349-52
59. Hahn WC, Stewart SA, Brooks MW, et al. Inhibition of telomerase limits the growth of human cancer cells. Nat Med 1999 Oct; 5 (10): 1164-70
60. Herbert B, Pitts AE, Baker SI, et al. Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci U S A 1999 Dec 7; 96 (25): 14276-81
61. Djojosubroto MW, Chin AC, Go N, et al. Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma. Hepatology 2005 Nov; 42 (5): 1127-36
62. Ozawa T, Gryaznov SM, Hu LJ, et al. Antitumor effects of specific telomerase inhibitor GRN163 in human glioblastoma xenografts. Neuro-oncol 2004 Jul; 6 (3): 218-26
63. Wang ES, Wu K, Chin AC, et al. Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma. Blood 2004 Jan 1; 103 (1): 258-66
64. Blasco MA, Lee HW, Hande MP, et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997 Oct 3; 91 (1): 25-34
65. Roth A, Yssel H, Pene J, et al. Telomerase levels control the lifespan of human T lymphocytes. Blood 2003 Aug 1; 102 (3): 849-57
66. Vulliamy T, Marrone A, Goldman F, et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001 Sep 27; 413 (6854): 432-5
67. Vulliamy T, Marrone A, Szydlo R, et al. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 2004 May; 36 (5): 447-9
68. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000 Sep; 110 (4): 768-79
69. Lundblad V, Blackburn EH. An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 1993 Apr 23; 73 (2): 347-60
70. Rizki A, Lundblad V. Defects in mismatch repair promote telomerase-independent proliferation. Nature 2001 Jun 7; 411 (6838): 713-6
71. Damm K, Hemmann U, Garin-Chesa P, et al. A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J 2001 Dec 17; 20 (24): 6958-68
72. Bechter OE, Zou Y, Walker W, et al. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res 2004 May 15; 64 (10): 3444-51
73. Elmore LW, Di X, Dumur C, et al. Evasion of a single-step, chemotherapy-induced senescence in breast cancer cells: implications for treatment response. Clin Cancer Res 2005 Apr 1; 11 (7): 2637-43
74. Xue W, Zender L, Miething C, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007 Feb 8; 445 (7128): 656-60
75. El-Daly H, Kull M, Zimmermann S, et al. Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532. Blood 2005 Feb 15; 105 (4): 1742-9
76. Gonzalez-Suarez E, Samper E, Flores JM, et al. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. Nat Genet 2000 Sep; 26 (1): 114-7
77. Cayuela ML, Flores JM, Blasco MA. The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression. EMBO Rep 2005 Mar; 6 (3): 268-74
78. Sarin KY, Cheung P, Gilison D, et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 2005 Aug 18; 436 (7053): 1048-52
79. Asai A, Oshima Y, Yamamoto Y, et al. A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res 2003 Jul 15; 63 (14): 3931-9
80. Herbert BS, Gellert GC, Hochreiter A, et al. Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 2005 Aug 4; 24 (33): 5262-8
81. Akiyama M, Hideshima T, Shammas MA, et al. Effects of oligonucleotide N3′→P5′ thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells. Cancer Res 2003 Oct 1; 63 (19): 6187-94
82. Dikmen ZG, Gellert GC, Jackson S, et al. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res 2005 Sep 1; 65 (17): 7866-73
83. Hochreiter AE, Xiao H, Goldblatt EM, et al. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin Cancer Res 2006 May 15; 12 (10): 3184-92
84. Jackson SR, Zhu CH, Paulson V, et al. Antiadhesive effects of GRN163L, an oligonucleotide N3′→P5′ thio-phosphoramidate targeting telomerase. Cancer Res 2007 Feb 1; 67 (3): 1121-9
85. Geron's GRN163L headed to phase I clinical trials in lung cancer patients [online]. Available from URL: http://cancerfocus.net/node/223 [Accessed 2007 Oct 25]
86. Geron Corporation announces multiple presentations on its telomerase inhibitor drug GRN163l at the AACR 2005 annual meeting. Press release [online]. Available from URL: http://www.geron.com/pressview.asp?id=710 [Accessed 2007 Oct 25]
87. Strahl C, Blackburn EH. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines. Mol Cell Biol 1996 Jan; 16 (1): 53-65
88. Naasani I, Seimiya H, Yamori T, et al. FJ5002: a potent telomerase inhibitor identified by exploiting the disease-oriented screening program with COMPARE analysis. Cancer Res 1999 Aug 15; 59 (16): 4004-11
89. Seimiya H, Oh-Hara T, Suzuki T, et al. Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991. Mol Cancer Ther 2002 Jul; 1 (9): 657-65
90. Smogorzewska A, de Lange T. Regulation of telomerase by telomeric proteins. Annu Rev Biochem 2004; 73: 177-208
91. Holt SE, Aisner DL, Baur J, et al. Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev 1999 Apr 1; 13 (7): 817-26
92. Seimiya H, Sawada H, Muramatsu Y, et al. Involvement of 14-3-3 proteins in nuclear localization of telomerase. EMBO J 2000 Jun 1; 19 (11): 2652-61
93. Seimiya H, Muramatsu Y, Ohishi T, et al. Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics. Cancer Cell 2005 Jan; 7 (1): 25-37
94. Blackburn EH. Telomere states and cell fates. Nature 2000 Nov 2; 408 (6808): 53-6
95. Mo Y, Gan Y, Song S, et al. Simultaneous targeting of telomeres and telomerase as a cancer therapeutic approach. Cancer Res 2003 Feb 1; 63 (3): 579-85
96. Parkinson GN, Lee MP, Neidle S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 2002 Jun 20; 417 (6891): 876-80
97. Burger AM, Dai F, Schultes CM, et al. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res 2005 Feb 15; 65 (4): 1489-96
98. Grand CL, Han H, Munoz RM, et al. The cationic porphyrin TMPyP4 downregulates c-MYC and human telomerase reverse transcriptase expression and inhibits tumor growth in vivo. Mol Cancer Ther 2002 Jun; 1 (8): 565-73
99. Shin-ya K, Wierzba K, Matsuo K, et al. Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J Amer Chem Soc 2001 Feb 14; 123 (6): 1262-3
100. Tahara H, Shin-Ya K, Seimiya H, et al. G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells. Oncogene 2006 Mar 23; 25 (13): 1955-66
101. Neidle S, Parkinson G. Telomere maintenance as a target for anticancer drug discovery. Nat Rev Drug Discov 2002 May; 1 (5): 383-93
102. Rezler EM, Bearss DJ, Hurley LH. Telomeres and telomerases as drug targets. Curr Opin Pharmacol 2002 Aug; 2 (4): 415-23
103. Gomez D, Paterski R, Lemarteleur T, et al. Interaction of telomestatin with the telomeric single-strand overhang. J Biol Chem 2004 Oct 1; 279 (40): 41487-94
104. Fukuda H, Katahira M, Tsuchiya N, et al. Unfolding of quadruplex structure in the G-rich strand of the minisatellite repeat by the binding protein UP1. Proc Natl Acad Sci U S A 2002 Oct 1; 99 (20): 12685-90
105. Rha SY, Izbicka E, Lawrence R, et al. Effect of telomere and telomerase interactive agents on human tumor and normal cell lines. Clin Cancer Res 2000 Mar; 6 (3): 987-93
106. Kim MY, Gleason-Guzman M, Izbicka E, et al. The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. Cancer Res 2003 Jun 15; 63 (12): 3247-56
107. Gomez D, Wenner T, Brassart B, et al. Telomestatin-induced telomere uncapping is modulated by POT1 through G-overhang extension in HT1080 human tumor cells. J Biol Chem 2006 Dec 15; 281 (50): 38721-9
108. Smogorzewska A, de Lange T. Different telomere damage signaling pathways in human and mouse cells. EMBO J 2002 Aug 15; 21 (16): 4338-48
109. Maida Y, Kyo S, Kanaya T, et al. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Oncogene 2002 Jun 13; 21 (26): 4071-9
110. Suenaga M, Yamaguchi A, Soda H, et al. Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity. Anticancer Res 2006 Sep-Oct; 26 (5A): 3387-91
111. Hansen NJ, Wylie RC, Phipps SM, et al. The low-toxicity 9-cis UAB30 novel retinoid down-regulates the DNA methyltransferases and has anti-telomerase activity in human breast cancer cells. Int J Oncol 2007 Mar; 30 (3): 641-50
112. Zhou C, Boggess JF, Bae-Jump V, et al. Induction of apoptosis and inhibition of telomerase activity by arsenic trioxide (As2O3) in endometrial carcinoma cells. Gynecol Oncol 2007 Apr; 105 (1): 218-22
113. Zhou C, Gehrig PA, Whang YE, et al. Rapamycin inhibits telomerase activity by decreasing the hTERT mRNA level in endometrial cancer cells. Mol Cancer Ther 2003 Aug; 2 (8): 789-95
114. Lindkvist A, Ivarsson K, Jernberg-Wiklund H, et al. Interferon-induced sensitization to apoptosis is associated with repressed transcriptional activity of the hTERT promoter in multiple myeloma. Biochem Biophys Res Commun 2006 Mar 24; 341 (4): 1141-8
115. He H, Xia HH, Wang JD, et al. Inhibition of human telomerase reverse transcriptase by nonsteroidal antiinflammatory drugs in colon carcinoma. Cancer 2006 Mar 15; 106 (6): 1243-9
116. Goytisolo FA, Samper E, Martin-Caballero J, et al. Short telomeres result in organismal hypersensitivity to ionizing radiation in mammals. J Exp Med 2000 Dec 4; 192 (11): 1625-36
117. Lee KH, Rudolph KL, Ju YJ, et al. Telomere dysfunction alters the chemotherapeutic profile of transformed cells. Proc Natl Acad Sci U S A 2001 Mar 13; 98 (6): 3381-6
118. Incles CM, Schultes CM, Kelland LR, et al. Acquired cellular resistance to flavopiridol in a human colon carcinoma cell line involves up-regulation of the telomerase catalytic subunit and telomere elongation: sensitivity of resistant cells to combination treatment with a telomerase inhibitor. Mol Pharmacol 2003 Nov; 64 (5): 1101-8
119. McCaul JA, Gordon KE, Clark LJ, et al. Telomerase inhibition and the future management of head-and-neck cancer. Lancet Oncol 2002 May; 3 (5): 280-8
120. Shay JW, Wright WE. Telomerase: a target for cancer therapeutics. Cancer Cell 2002 Oct; 2 (4): 257-65
121. Singh M, Johnson L. Using genetically engineered mouse models of cancer to aid drug development: an industry perspective. Clin Cancer Res 2006 Sep 15; 12 (18): 5312-28
122. Lou H, Dean M. Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 2007 Feb 26; 26 (9): 1357-60
123. Kipling D, Cooke HJ. Hypervariable ultra-long telomeres in mice. Nature 1990 Sep 27; 347 (6291): 400-2
124. Hockemeyer D, Daniels JP, Takai H, et al. Recent expansion of the telomeric complex in rodents: two distinct POT1 proteins protect mouse telomeres. Cell 2006 Jul 14; 126 (1): 63-77
125. Horikawa I, Chiang YJ, Patterson T, et al. Differential cis-regulation of human versus mouse TERT gene expression in vivo: identification of a human-specific repressive element. Proc Natl Acad Sci U S A 2005 Dec 20; 102 (51): 18437-42
126. Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci U S A 1995 May 23; 92 (11): 4818-22
127. Nagase H, Bryson S, Cordell H, et al. Distinct genetic loci control development of benign and malignant skin tumours in mice. Nat Genet 1995 Aug; 10 (4): 424-9
128. Liu Y, Snow BE, Hande MP, et al. The telomerase reverse transcriptase is limiting and necessary for telomerase function in vivo. Curr Biol 2000 Nov 16; 10 (22): 1459-62