Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers

Cancer Science

Volumn 99, Issue 8, 2008, Pages 1528-1538

  Kyo, Satoru ^a   Takakura, Masahiro ^a   Fujiwara, Toshiyoshi ^b   Inoue, Masaki ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b OKAYAMA UNIVERSITY HOSPITAL   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 2; ADENOVIRUS VECTOR; CONTRAST MEDIUM; DOCETAXEL; E1A ASSOCIATED P300 PROTEIN; E1B PROTEIN; ESTROGEN RECEPTOR ALPHA; GREEN FLUORESCENT PROTEIN; HISTONE ACETYLTRANSFERASE; HYPOXIA INDUCIBLE FACTOR 1; IRINOTECAN; METHIONINE; MYC PROTEIN; NAVELBINE; OBP 301; OBP 401; ONCOLYTIC ADENOVIRUS; PROTEIN P53; TELOMELYSIN; TELOMERASE REVERSE TRANSCRIPTASE; TELOMESCAN; TRANSCRIPTION FACTOR SP1; WT1 PROTEIN;

ANTINEOPLASTIC ACTIVITY; BINDING AFFINITY; BINDING SITE; CANCER DIAGNOSIS; CANCER GENE THERAPY; CANCER SCREENING; CHROMATIN STRUCTURE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIAGNOSTIC IMAGING; DNA METHYLATION; DNA MODIFICATION; DRUG DOSE ESCALATION; DRUG EFFICACY; E BOX ELEMENT; GENE ACTIVATION; GENE ACTIVITY; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; GENE TARGETING; HORMONAL REGULATION; HUMAN; LYMPH NODE METASTASIS; MONOTHERAPY; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; TRANSCRIPTION REGULATION; TUMOR; UPREGULATION;

ADENOVIRIDAE; ANIMALS; GENE EXPRESSION REGULATION, NEOPLASTIC; GREEN FLUORESCENT PROTEINS; HUMANS; LYMPHATIC METASTASIS; MICE; NEOPLASMS; PROMOTER REGIONS (GENETICS); TELOMERASE;

EID: 49749139661     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/j.1349-7006.2008.00878.x     Document Type: Review

References (118)

1. Kim NW, Piatyszek MA, Prowse KR et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266: 2011-15.
2. Rudolph KL, Chang S, Lee HW et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 1999; 96: 701-12.
3. Chin L, Artandi SE, Shen Q et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 1999; 97: 527-38.
4. Artandi SE, DePinho RA. Mice without telomerase: What can they teach us about human cancer? Nat Med 2000; 6: 852-5.
5. Meyerson M, Counter CM, Eaton EN et al. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 1997; 90: 785-95.
6. Nakamura TM, Morin GB, Chapman KB et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997; 277: 955-9.
7. Bodnar AG, Ouellette M, Frolkis M et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279: 349-52.
8. Nakayama J, Tahara H, Tahara E et al. Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nat Genet 1998; 18: 65-8.
9. Takakura M, Kyo S, Kanaya T, Tanaka M, Inoue M. Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res 1998; 58: 1558-61.
10. Kyo S, Kanaya T, Takakura M, Tanaka M, Inoue M. Human telomerase reverse transcriptase as a critical determinant of telomerase activity in normal and malignant endometrial tissues. Int J Cancer 1999; 80: 60-3.
11. Kanaya T, Kyo S, Takakura M, Ito H, Namiki M, Inoue M. hTERT is a critical determinant of telomerase activity in renal-cell carcinoma. Int J Cancer 1998; 78: 539-43.
12. Kyo S, Kanaya T, Takakura M et al. Expression of human telomerase subunits in ovarian malignant, borderline and benign tumors. Int J Cancer 1999; 80: 804-9.
13. Takakura M, Kyo S, Kanaya T et al. Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 1999; 59: 551-7.
14. Horikawa I, Cable PL, Afshari C, Barrett JC. Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res 1999; 59: 826-30.
15. Cong YS, Wen J, Bacchetti S. The human telomerase catalytic subunit hTERT. Organization of the gene and characterization of the promoter. Hum Mol Genet 1999; 8: 137-42.
16. Wang J, Xie LY, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes Dev 1998; 12: 1769-174.
17. Wu KJ, Grandori C, Amacker M et al. Direct activation of TERT transcription by c-MYC. Nature Genet 1999; 21: 220-4.
18. Greenberg RA, O'Hagan RC, Deng H et al. Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene 1999; 18: 1219-26.
19. Kyo S, Takakura M, Taira T et al. Spl cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res 2000; 28: 669-77.
20. Kirkpatrick KL, Ogunkolade W, Elkak AE et al. hTERT expression in human breast cancer and non-cancerous breast tissue: Correlation with tumour stage and c-Myc expression. Breast Cancer Res Treat 2003; 77: 277-84.
21. Günes C, Lichtsteiner S, Vasserot AP, Englert C. Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1. Cancer Res 2000; 60: 2116-21.
22. Xu D, Popov N, Hou M et al. Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Acad Sci USA 2001; 98: 3826-31.
23. Deng WG, Jayachandran G, Wu G, Xu K, Roth JA, Ji L. Tumor-specific activation of human telomerase reverses transcriptase promoter activity by activating enhancer-binding protein-2beta in human lung cancer cells. J Biol Chem 2007; 282: 26460-70.
24. Yatabe N, Kyo S, Maida Y et al. HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene 2004; 23: 3708-15.
25. Nishi H, Nakada T, Kyo S, Inoue M, Shay JW, Isaka K. Hypoxia-inducible factor mediates upregulation of telomerase (hTERT). Mol Cell Biol 2004; 24: 6076-83.
26. Koshiji M, Kageyama Y, Pete EA, Horikawa I, Barrett JC, Huang LE. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc. EMBO J 2004; 23: 1949-56.
27. Lou F, Chen X, Jalink M et al. The opposing effect of hypoxia-inducible factor-2alpha on expression of telomerase reverse transcriptase. Mol Cancer Res 2007; 5: 793-800.
28. Takakura M, Kyo S, Inoue M, Wright WE, Shay JW. The function of AP1 on transcription of telomerase reverse transcriptase gene (TERT) in human and mouse cell. Mol Cell Biol 2005; 18: 8037-43.
29. Kyo S, Takakura M, Kanaya T et al. Estrogen activates telomerase. Cancer Res 1999; 59: 5917-21.
30. Misiti S, Nanni S, Fontemaggi G et al. Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells. Mol Cell Biol 2000; 20: 3764-71.
31. Kimura A, Ohmichi M, Kawagoe J et al. Induction of hTERT expression and phosphorylation via Akt cascade by estrogen in human ovarian cancer cell lines. Oncogene 2004; 23: 4505-15.
32. Wang Z, Kyo S, Maida Y et al. Tamoxifen regulates human telomerase reverse transcriptase (hTERT) gene expression differently in breast and endometrial cancer cells. Oncogene 2002; 21: 3517-24.
33. Guo C, Armbruster BN, Price DT, Counter CM. In vivo regulation of hTERT expression and telomerase activity by androgen. J Urol 2003; 170: 615-8.
34. Wang Z, Kyo S, Takakura M et al. Progesterone regulates human telomerase reverse transcriptase (hTERT) gene expression via activation of MAP kinase signaling pathway. Cancer Res 2000; 60: 5376-81.
35. Hiyama K, Hirai Y, Kyoizumi S et al. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 1995; 155: 3711-5.
36. Kyo S, Takakura M, Kohama T, Inoue M. Telomerase activity in human endometrium. Cancer Res 1997; 57: 610-14.
37. Holt SE, Wright WE, Shay JW. Regulation of telomerase activity in immortal cell lines. Mol Cell Biol 1996; 16: 2932-9.
38. Maida M, 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; 21: 4071-9.
39. Yang H, Kyo S, Takakura M, Sun L. Autocrine transforming growth factor b suppresses activity and hTERT transcription in human cancer cells. Cell Growth Differ 2001; 12: 119-27.
40. Cerezo A, Kalthoff H, Schuermann M, Schäfer B, Boukamp P. Dual regulation of telomerase activity through c-Myc-dependent inhibition and alternative splicing of hTERT. J Cell Sci 2002; 115: 1305-12.
41. Hu B, Tack DC, Liu T, Wu Z, Ullenbruch MR, Phan SH. Role of Smad3 in the regulation of rat telomerase reverse transcriptase by TGFbeta. Oncogene 2006; 25: 1030-41.
42. Li H, Xu D, Li J, Berndt MC, Liu JP. Transforming growth factor beta suppresses human telomerase reverse transcriptase (hTERT) by Smad3 interactions with c-Myc and the hTERT gene. J Biol Chem 2006; 281: 25588-600.
43. Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell 2003; 113: 881-9.
44. Lacerte A, Korah J, Roy M, Yang XJ, Lemay S, Lebrun JJ. Transforming growth factor-beta inhibits telomerase through SMAD3 and E2F transcription factors. Cell Signal 2008; 20: 50-9.
45. Dyson N, Howley PM, Münger K, Harlow E. The human papilloma virus-16, E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989, 243: 934-7.
46. Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18E6 proteins with p53. Science 1990; 248: 76-9.
47. Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993; 75: 495-505.
48. Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 1990; 63: 1129-36.
49. Klingelhutz AJ, Foster SA, McDougall JK. Telomerase activation by the E6 gene product of human papillomavirus type 16. Nature 1996; 380: 79-82.
50. Wang J, Xie LY, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes Dev 1998; 12: 1769-74.
51. Oh ST, Kyo S, Laimins LA. Telomerase activation by HPV-16 E6: Induction of hTERT expression through Myc and GC-rich Sp1 binding sites. J Virol 2001; 75: 5559-66.
52. Gewin L, Galloway DA. E box-dependent activation of telomerase by human papillomavirus type 16, E6 does not require induction of c-myc. J Virol 2001; 75: 7198-201.
53. Veldman T, Horikawa I, Barrett JC, Schlegel R. Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16, E6 oncoprotein. J Virol 2001; 75: 4467-72.
54. Gewin L, Myers H, Kiyono T, Galloway DA. Identification of a novel telomerase repressor that interacts with the human papillomavirus type-16, E6/E6-AP complex. Genes Dev 2004; 18: 2269-82.
55. Goueli BS, Janknecht R. Upregulation of the catalytic telomerase subunit by the transcription factor ER81 and oncogenic HER2/Neu, ras, or raf. Mol Cell Biol 2004; 24: 25-35.
56. Shin KH, Kang MK, Dicterow E et al. Hypermethylation of the hTERT promoter inhibits the expression of telomerase activity in normal oral fibroblasts and senescent normal oral keratinocytes. Br J Cancer 2003; 89: 1473-8.
57. Lopatina NG, Poole JC, Saldanha SN et al. Control mechanisms in the regulation of telomerase reverse transcriptase expression in differentiating human teratocarcinoma cells. Biochem Biophys Res Commun 2003; 306: 650-9.
58. Liu L, Saldanha SN, Pate MS et al. Epigenetic regulation of human telomerase reverse transcriptase promoter activity during cellular differentiation. Genes Chromosomes Cancer 2004; 41: 26-37.
59. Devereux TR, Horikawa I, Anna CH, Annab LA, Afshari CA, Barrett JC. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res 1999; 59: 6087-90.
60. Dessain SK, Yu H, Reddel RR, Beijersbergen RL, Weinberg RA. Methylation of the human telomerase gene CpG island. Cancer Res 2000; 60: 537-41.
61. Guilleret I, Yan P, Grange F, Braunschweig R, Bosman FT, Benhattar J. Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int J Cancer 2002; 101: 335-41.
62. Zinn RL, Pruitt K, Eguchi S, Baylin SB, Herman JG. hTERT is expressed in cancer cell lines despite promoter DNA methylation by preservation of unmethylated DNA and active chromatin around the transcription start site. Cancer Res 2007; 67: 194-201.
63. Stein GS, Montecino M, van Wijnen AJ, Stein JL, Lian JB. Nuclear structure-gene expression interrelationships: Implications for aberrant gene expression in cancer. Cancer Res 2000; 60: 2067-76.
64. Cong YS, Bacchetti S. Histone deacetylation is involved in the transcriptional repression of hTERT in normal human cells. J Biol Chem 2000; 275: 35665-8.
65. Takakura M, Kyo S, Sowa Y et al. Telomerase activation by histone deacetylase inhibitor in normal cells. Nucleic Acids Res 2001; 29: 3006-11.
66. Doetzlhofer A, Rotheneder H et al. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol Cell Biol 1999; 19: 5504-11.
67. Suzuki T, Kimura A, Nagai R, Horikoshi M. Regulation of interaction of the acetyltransferase region of p300 and the DNA-binding domain of Sp1 on and through DNA binding. Genes Cells 2000; 5: 29-41.
68. Oh S, Song YH, Yim J, Kim TK. Identification of Mad as a repressor of the human telomerase (hTERT) gene. Oncogene 2000; 19: 1485-90.
69. Atkinson SP, Hoare SF, Glasspool RM, Keith WN. Lack of telomerase gene expression in alternative lengthening of telomere cells is associated with chromatin remodeling of the hTR and hTERT gene promoters. Cancer Res 2005; 65: 7585-90.
70. Liu C, Fang X, Ge Z et al. The telomerase reverse transcriptase (hTERT) gene is a direct target of the histone methyltransferase SMYD3. Cancer Res 2007; 67: 2626-31.
71. Kanaya T, Kyo S, Hamada K et al. Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription. Clin Cancer Res 2000; 6: 1239-47.
72. Xu D, Wang Q, Gruber A et al. Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells. Oncogene 2000; 19: 5123-33.
73. Oh S, Song Y, Yim J, Kim TK. The Wilms' tumor 1 tumor suppressor gene represses transcription of the human telomerase reverse transcriptase gene. J Biol Chem 1999; 274: 37473-8.
74. Fujimoto K, Kyo S, Takakura M et al. Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: Possible role of MZF-2 in transcriptional repression of hTERT. Nucleic Acids Res 2000; 28: 2557-62.
75. Ikeda N, Uemura H, Ishiguro H et al. Combination treatment with 1alpha, 25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells. Mol Cancer Ther 2003; 2: 739-46.
76. Oshimura M, Barrett JC. Multiple pathways to cellular senescence: Role of telomerase repressors. Eur J Cancer 1997; 33: 710-5.
77. Horikawa I, Oshimura M, Barrett JC. Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence. Mol Carcinogen 1998; 22: 65-72.
78. Tanaka H, Shimizu M, Horikawa I, Kugoh H, Yokota J, Barrett JC, Oshimura M. Evidence for a putative telomerase repressor gene in the 3p14.2-p21.1 region. Genes Chromosomes Cancer 1998; 23: 123-33.
79. Cuthbert AP, Bond J, Trott DA et al. Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells. J Natl Cancer Inst 1999; 91: 37-45.
80. Ducrest AL, Amacker M, Mathieu YD et al. Regulation of human telomerase activity: Repression by normal chromosome 3 abolishes nuclear telomerase reverse transcriptase transcripts but does not affect c-Myc activity. Cancer Res 2001; 61: 7594-602.
81. Backsch. C, Wagenbach N, Nonn M et al. Microcell-mediated transfer of chromosome 4 into HeLa cells suppresses telomerase activity. Genes Chromosomes Cancer 2001; 31: 196-8.
82. Steenbergen RDM, Kramer D, Meijer CJ et al. Telomerase suppression by chromosome 6 in a human papillomavirus type 16-immortalized keratinocyte cell line and in a cervical cancer cell line. J Natl Cancer Inst 2001; 93: 865-72.
83. Nakabayashi K, Ogino H, Michishita E, Satoh N, Ayusawa D. Introduction of chromosome 7 suppresses telomerase with shortening of telomeres in a human mesothelial cell line. Exp Cell Res 1999; 252: 376-82.
84. Nishimoto A, Miura N, Horikawa I et al. Functional evidence for a telomerase repressor gene on human chromosome 10p15.1. Oncogene 2001; 20: 828-35.
85. Yang X, Tahin Q, Hu YF et al. Functional roles of chromosomes 11 and 17 in the transformation of human breast epithelial cells in vitro. Int J Oncol 1999; 15: 629-38.
86. Horikawa I, Cable PL, Mazur SJ, Appella E, Afshari CA, Barrett JC. Downstream E-box-mediated regulation of the human telomerase reverse transcriptase (hTERT) gene transcription: Evidence for an endogenous mechanism of transcriptional repression. Mol Biol Cell 2002; 13: 2585-97.
87. Vile RG, Hart IR. In vitro and in vivo targeting of gene expression to melanoma cells. Cancer Res 1993; 53: 962-7.
88. Osaki T, Tanio Y, Tachibana I et al. Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene. Cancer Res 1994; 54: 5258-61.
89. Chen L, Chen D, Manome Y, Dong Y, Fine HA, Kufe DW. Breast cancer selective gene expression and therapy mediated by recombinant adenoviruses containing the DF3/MUC1 promoter. J Clin Invest 1995; 96: 2775-82.
90. Parr MJ, Manome Y, Tanaka T et al. A. Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector. Nat Med 1997; 3: 1145-9.
91. Gu J, Kagawa S, Takakura M et al. Tumor-specific transgene expression from hTERT promoter: Targeting pharmaceutical effects of the Bax gene to cancer. Cancer Res 2000; 60: 5359-64.
92. Komata T, Koga S, Hirohata S et al. A novel treatment of human malignant gliomas in vitro and in vivo: FADD gene transfer under the control of the human telomerase reverse transcriptase gene promoter. Int J Oncol 2001; 19: 1015-20.
93. Koga S, Hirohata S, Kondo Y et al. FADD gene therapy using the human telomerase catalytic subunit (hTERT) gene promoter to restrict induction of apoptosis to tumors in vitro and in vivo. Anti Cancer Res 2001; 21: 1937-43.
94. Komata T, Kondo Y, Kanzawa T et al. Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (hTERT) gene. Cancer Res 2001; 61: 5796-802.
95. Takeuchi H, Kanzawa T, Kondo Y et al. Combination of caspase transfer using the human telomerase reverse transcriptase promoter and conventional therapies for malignant glioma cells. Int J Oncol 2004; 25: 57-63.
96. Takeda T, Inaba H, Yamazaki M et al. Tumor-specific gene therapy for undifferentiated thyroid carcinoma utilizing the telomerase reverse transcriptase promoter. J Clin Endcrinol Metab 2003; 88: 3531-8.
97. Lin T, Huang X, Gu J et al. Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 2002; 21: 8020-8.
98. Nakamura M, Kyo S, Kanaya T et al. hTERT-promoter-based tumor specific expression of MCP-1 effectively sensitize cervical cancer cells to a low dose of cisplatin. Cancer Gene Ther 2004; 11: 1-7.
99. Gu J, Andreeff M, Roth JA, Fang B. hTERT promoter induces tumor-specific Bax gene expression and cell killing in syngenic mouse tumor model and prevents systemic toxicity. Gene Ther 2002; 9: 30-7.
100. Rodriguez R, Schuur ER, Lim HY, Henderson GA, Simons JW, Henderson DR. Prostate attenuated replication competent adenovirus (ARCA) CN706: A selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. Cancer Res 1997; 57: 2559-63.
101. Kurihara T, Brough DE, Kovesdi I, Kufe DW. Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen. J Clin Invest 2000; 106: 763-71.
102. Matsubara S, Wada Y, Gardner TA et al. A conditional replication-competent adenoviral vector, Ad-OC-E1a, to cotarget prostate cancer and bone stroma in an experimental model of androgen-independent prostate cancer bone metastasis. Cancer Res 2001; 61: 6012-9.
103. Peng XY, Won JH, Rutherford T et al. The use of the 1-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines. Cancer Res 2001; 61: 4405-13.
104. Adachi Y, Reynolds PN, Yamamoto M et al. A midkine promoter-based conditionally replicative adenovirus for treatment of pediatric solid tumors and bone marrow tumor purging. Cancer Res 2001; 61: 7882-8.
105. Tsukuda K, Wiewrodt R, Molnar-Kimber K, Jovanovic VP, Amin KM. An E2F-responsive replication-selective adenovirus targeted to the defective cell cycle in cancer cells: Potent antitumoral efficacy but no toxicity to normal cell. Cancer Res 2002; 62: 3438-47.
106. Kawashima T, Kagawa S, Kobayashi N et al. Telomerase-specific replication selective virotherapy for human cancer. Clin Cancer Res 2004; 10: 285-92.
107. Wirth T, Zender L, Schulte B et al. A telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer. Cancer Res 2003; 63: 3181-8.
108. Lanson NA Jr, Friedlander PL, Schwarzenberger P, Kolls JK, Wang G. Replication of an adenoviral vector controlled by the human telomerase reverse transcriptase promoter causes tumor-selective tumor lysis. Cancer Res 2003; 63: 7936-41.
109. Irving J, Wang Z, Powell S et al. Conditionally replicative adenovirus driven by the human telomerase promoter provides broad-spectrum antitumor activity without liver toxicity. Cancer Gene Ther 2004; 11: 174-85.
110. Taki M, Kagawa S, Nishizaki M et al. Enhanced oncolysis by OBP-405, a tropism-modified telomerase-specific replication-selective adenoviral agent. Oncogene 2005; 24: 3130-40.
111. Fujiwara T, Kagawa S, Kishimoto H et al. Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent OBP-401 with docetaxel: preclinical evaluation of chemovirotherapy. Int J Cancer 2006; 119: 432-40.
112. Wirth T, Kühnel F, Fleischmann-Mundt B et al. Telomerase-dependent virotherapy overcomes resistance of hepatocellular carcinomas against chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand by elimination of Mcl-1. Cancer Res 2005; 65: 7393-402.
113. Kitazono M, Goldsmith ME, Aikou T, Bates S, Fojo T. Enhanced adenovirus transgene expression in malignant cells treated with the histone deacetylase inhibitor FR901228. Cancer Res 2001; 61: 6328-30.
114. Watanabe T, Hioki M, Fujiwara T et al. Histone deacetylase inhibitor FR901228 enhances the antitumor effect of telomerase-specific replication-selective adenoviral agent OBP-301 in human lung cancer cells. Exp Cell Res 2006; 312: 256-65.
115. Umeoka T, Kawashima T, Kagawa S et al. Visualization of intrathoracically disseminated solid tumors in mice with optical imaging by telomerase-specific amplification of a transferred green fluorescent protein gene. Cancer Res 2004; 64: 6259-65.
116. Kishimoto H, Kojima T, Watanabe Y et al. A novel in vivo imaging of lymph node metastasis with telomerase-specific replication-competent adenovirus containing green fluorescent protein gene. Nat Med 2006; 12: 1213-9.
117. Masutomi K, Yu EY, Khurts S et al. Telomerase maintains telomere structure in normal human cells. Cell 2003; 114: 241-53.
118. + cells by an adenovirus type 35 vector. Gene Ther 2003; 10: 1041-8.