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2016 | 42 | 87-100
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Activities of human telomerase in cancer development, detection and therapeutics - A Review

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EN
Telomeres are the specialized nucleoprotein structures associated with eukaryotic chromosomal ends, which are essential for maintaining the stability of the linear eukaryotic chromosomes. Progressive telomere shortening is an inevitable occurrence in normal somatic cells due to the end-replication problem leading to limited replication efficiency. The hallmark characteristics of human cancer cells include infinite reproductive potential, uncontrolled proliferation and immortality. These abilities of transformed cancerous cells are mainly due to the maintenance of their telomeres since degradation of chromosomal telomeric ends leads to cellular senescence or death. Thus telomere biology is important in the study of human cancer development. The mechanism by virtue the cancer cells are able to divide indefinitely is by maintaining telomeres. Activity of telomerase, a telomere-elongating ribonucleoprotein reverse transcriptase enzyme, is responsible for inducing the property of immortality to cancer cells. In humans nearly about 80% to 90% cancer cells activate telomerase and elongate their telomeres to overcome the end-replication problem. Telomere shortening suppresses cancer formation in contrast according to certain reports it sometimes promotes genomic instability which leads to enhancement of carcinogenesis and consequently the development of malignancy. Majority of cancer cells activate telomerase, but it remains mysterious as to find the reasons of the fact that certain cancer cells often show shorter telomeres in comparison to the cells in the surrounding normal tissues. This controversial role of telomerase associated with certain transformed cells leading to the cancerous state in relation to its role in normal cells is an interesting field to study which points out to the fact of development of cancer cells targeting drugs based on telomerase activities as an alternative weapon in combating against this dreaded human disease. The present review focuses on the activity of telomerase in telomere maintenance in the development of cancerous cells in humans, the use of telomerase as an assay technique for cancer detection as well as the anti-cancer therapeutic approach of targeting the telomerase in the current era of treatment of human cancer.
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Year
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42
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87-100
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author
  • Department of Biological Sciences, Presidency University Kolkata, India
  • Department of Microbiology, Scottish Church College, Kolkata - 700006, India
References
  • [1] Bacchetti S, Counter C (1995). Telomeres and telomerase in human cancer [Review], Int J Oncol, 7: 423-432.
  • [2] Bianchi A, de Lange T (1999). Ku binds telomeric DNA in vitro, J Biol Chem, 274: 21223-21227.
  • [3] Bianchi A, Stansel RM, Fairall L, Griffith JD, Rhodes D, de Lange T (1999). TRF1 binds a bipartite telomeric site with extreme spatial flexibility, EMBO J, 18: 5735-5744.
  • [4] Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E (1997). Telomeric localization of TRF2, a novel human telobox protein. Nature Genet, 17: 236-239.
  • [5] Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichsteiner S, Wright WE (1998). Extension of life-span by introduction of telomerase into normal human cells, Science, 279: 349-352.
  • [6] Broccoli D, Smogorzewska A, Chong L, de Lange T (1997). Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2, Nature Genet, 17: 231-235.
  • [7] Byran TM, Englezou A, Gupta J, Bachetti S, Reddel RR (1995). Telomere elongation in immortal human cell without detectable telomerase activity. EMBO J, 14: 4240-4248.
  • [8] Chadeneau C, Hay K, Hirte H, Gallinger S, Bacchetti S (1995). Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res, 55: 2533-2536.
  • [9] Chen JL, Blasco MA, Greider CW (2000). Secondary structure of vertebrate telomerase RNA. Cell, 100: 503-514.
  • [10] Chong L, van Steensel B, Broccoli D, Erdjument – Bromage H, Hanish J, Tempst P, de Lange T (1995). A human telomeric protein. Science, 270: 1663-1667.
  • [11] Cooke HJ, Smith BA (1986). Variability at the telomeres of the human X/Y pseudoautosomal region. Cold Spring Harbor Symp Quant Biol, L1: 213-219.
  • [12] Cong Y, Shay JW (2008). Actions of human telomerase beyond telomeres. Cell Re., 18: 725-732.
  • [13] Counter CM, A vilion AA, LeFeuvre CE, et al., (1992). Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J, 11: 1921-1929.
  • [14] Counter CM, Hirte HW, Bacchetti S, Harley C. (1994). Telomerase in human ovarian carcinoma. Proc Natl Acad Sci USA, 91: 2900-2904.
  • [15] de Lange T (1992). Human telomeres are attached to the nuclear matrix. EMBO J, 11: 717–24.
  • [16] Demidov VV, Potaman VN, Frank-Kamenetskii MD, Egholm M, et al., (1994). Stability of peptide nucleic acids in human serum and cellular extracts. Biochem Pharmaco, 48: 1310-1313.
  • [17] Feng J, Funk WD, Wang SS, Weinrich SL, Avilion AA, Chiu CP, Adams RR, Chang E, et al., (1995). The RNA component of human telomerase. Science, 269: 1236-1241.
  • [18] Ford LP, Myoung J, Wright WE, Shay JW (2000). Heterogeneous nuclear ribonucleoproteins C1 and C2 associate with human telomerase. Mol Cell Biol, 20: 9084-9091.
  • [19] Ford LP, Shay JW, Wright WE (2001). The La antigen associates with human telomerase ribonucleoprotein and influences telomere length in vivo. RNA. In press.
  • [20] Gilley D, Blackburn EH (1999). The telomerase RNA pseudoknot is critical for the stability for the stable assembly of a catalytically active ribonucleoprotein. Proc Natl Acad Sci USA, 96: 6621-6625.
  • [21] Greider CW, Blackburn EH (1987). The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell, 51: 87-898.
  • [22] Greider CW (1996). Telomere length regulation. Annu Rev Biochem, 65: 337-365.
  • [23] Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999). Mammalian telomeres end in a large duplex loop. Cell, 97: 503-514.
  • [24] Harley CB (2008). Telomerase and cancer therapeutics. Nat Rev Cancer, 8: 167-179.
  • [25] Harley CB, Futcher AB, Greider CW (1990). Telomeres shorten during aging of human fibroblasts. Nature, 345: 458-460.
  • [26] Hayflick L, Moorhead LS (1961). The serial culture of diploid and transformed human fibroblasts. Exp Cell Res, 25: 585-621.
  • [27] Hiyama E, Hiyama K, Yokoyama T, Ichikawa T, Matsuura Y (1992). Length of telomeric repeats in neuroblastoma; correlation with prognosis and other biological characteristics. Jpn J Cancer Res, 83: 159-164.
  • [28] Hiyama K, Hiyama E, Ishioka S, Yamakido M, Inai K, Gazdar A, et al., (1995). Telomerase activity in small-cell and non-small-cell lung cancers. J Natl Cancer Inst, 87: 895-902.
  • [29] Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, Piatyszek M, et al., (1995). Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol, 155: 3711-3715.
  • [30] Hiyama E, Hiyama K, Yokoyama T, Matsuura Y, Piatyszek M, Shay J (1995). Correlating telomerase activity levels with human neuroblastoma outcomes. Nature Med, 1: 249-255.
  • [31] Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, Murakami Y, et al., (1995). Telomerase activity in gastric cancer. Cancer Res, 55: 3258-3262.
  • [32] Hsu HL, Gilley D, Galande SA, Hande MP, Allen B, Kim SH, Li GC, Campisi J, Kohwi-Shigematsu T, Chen DJ (2000). Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev, 14: 2807-2812.
  • [33] Hiyama E, Gollahon L, Kataoka T, Kuroi K, Yokoyama T, Gazdar AF, et al., (1996). Telomerase activity in human breast tumors. J Natl Cancer Inst, 17: 116-122.
  • [34] Kalluri R (1996). Telomere (telomerase) hypothesis of aging and immortalization. Indian J Biochem Biophys, 33: 88-92.
  • [35] Kanaya T, Kyo S, Hamada K, et al., (2000). Adenoviral expression of p53 represses telomerase activity througy down- regulation of human telomerase reverse transcriptase transcription. Clin Cancer Res, 6: 1239-1247.
  • [36] Katinka M, Bourgain F (1992). Interstitial telomeres are hotspots for illegitimate recombination with DNA molecules injected into the macronucleus of Paramoecium primaurelia. EMBO J, 11: 725-732.
  • [37] Kim SH, Kaminker P, Campisi J (1999). TIN2, a new regulator of telomere length in human cells. Nature Genet, 23: 405-412.
  • [38] Kim NW, Piatyszek MA, Prowse KR, et al., (1994). Specific association of human telomerase activity with immortal cells and cancer. Science, 266: 2011-2015.
  • [39] Kondo S, Kondo S, Tanaka Y, et al., (1998). Targeted therapy of human malignant glioma in a mouse model by 2, 5-A antisense directed against telomerase RNA. Oncogene, 16: 3323-3330.
  • [40] Kufel J, Allmang C, Chanfreau G, Petfalski E, Lafontaine DL, Tollervey D (2000). Precursors to the U3 small nucleolar RNA lack small nucleolar RNP proteins but are stabilized by La binding. Mol Cell Biol, 20: 5415-5424.
  • [41] Langford L, Piatyszek M, Xu R, Schold S, Shay J (1995). Telomerase activity in human brain tumours. Lancet, 346: 1267-1268.
  • [42] Li BB, Oestreich S, de Lange T (2000). Identification of human Rap1: Implications for telomere evolution. Cell, 101: 471-483.
  • [43] Lodish H, Kaiser CA, Bretscher A, Amon A, Berk A, Krieger M, Ploegh H, Scott MP (2013). Molecular cell biology. W. H. Freeman and Company New York, Macmillan. 7th Edition.
  • [44] Luke B, Lingner J (2009). TERRA: telomeric repeat containing RNA. EMBO J, 28: 2503-2520.
  • [45] Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, Kasim V, Hayashizaki Y, Hahn WC, Mashutomi K (2009). An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature, 461: 230-235.
  • [46] Mitchell JR, Cheng J, Collins K (1999). A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3΄ end. Mol Cell Biol, 19: 567-576.
  • [47] Morin GB (1989). The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell, 59: 521-529.
  • [48] Morin GB (1995). Is telomerase a universal cancer target? J Natl Cancer Inst, 859-860.
  • [49] Mu J, Wei LX (2002). Telomere and telomerase in oncology. Cell Res, 12: 1-7.
  • [50] Odagiri E, Kanda N, Jibiki K, Demura R, Aikawa E, Demura H (1994). Reduction of telomeric length and c- erbB-2 gene amplification in human breast cancer, fibroadenoma and gynecomastia. Cancer, 73: 2978-2984.
  • [51] Ohyashiki J, Ohyashiki K, Fujimura T, Kawakubo K, Shimamoto T, Iwabuchi A, Toyama K (1994). Telomere shortening associated with disease evolution patterns in myelodysplastic syndromes. Cancer Res, 54: 3557-3560.
  • [52] Olovnikov AM (1973). A theory of marginotomy: the incomplete copying of template margin in enzymatic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol, 41: 181-190.
  • [53] Pannone BK, Xue D, Wolin SL (1998). A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is molecular chaperone for RNA polymerase III transcripts. EMBO J, 17: 7442-7453.
  • [54] Parkinson GN, Lee MPH, Neidle S (2002). Crystal structure of parallel quadruplexes from human telomeric DNA. Nature, 417: 876-880.
  • [55] Poreboma C, Scheel C, Hero B, et al., (2000). Telomerase activity and telomerase subunit gene expression patterns in neuroblastoma:a molecular and immunohistochemical study establishing prognostic tools for fresh-frozen and paraffin-embedded tissues. J of Clin Oncol, 18(13): 2582-2592.
  • [56] Riou JF, Guitat L, Mailliet P, Laoui A, Renou E, Petitegenet O, Megnin-Chanet F, Helene C, Mergny JL (2002). Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands. Proc Natl Acad Sci USA, 99: 2672-2677.
  • [57] Schoeftner S, Blasco MA (2009). A higher order of telomere regulation : telomeric heterochromatin and telomeric RNAs . EMBO J, 28: 2323-2336.
  • [58] Schwartz H, Juliao S, Sciadini M, Miller L, Butler M (1995). Telomerase activity and oncogenesis in giant cell tumors of bone. Cancer, 75: 1094-1099.
  • [59] Shay JW (1999). At end of the millennium a view of the end. Nature Genet, 23: 382-383.
  • [60] Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer 1997; 33: 787-91.
  • [61] Shay JW, Keith WM (2008). Targeting telomerase for cancer therapeutics. Br J Cancer, 98: 677-683.
  • [62] Siddiqui–Jain A, Grand CL, Bearss DJ, Hurley LH (2002). Direct evidence for G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc Natl Acad Sci USA, 99: 11593-11598.
  • [63] Smith S, de Lange T (2000). Tankyrase promotes telomere elongation in human cells. Curr Biol, 10, 1299-1302.
  • [64] Smith S, de Lange T (1999) Cell cycle dependent localization of the telomeric PARP, tankyrase to nuclear complexes and centrosomes. J. Cell Sci. 112: 3649-3656.
  • [65] Smith S, Giriat I, Schmitt A, de Lange T (1998). Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science, 282: 1484-1487.
  • [66] Smith J, Yeh G (1992). Telomere reduction in endometrial adenocarcinoma. Am J Obstet Gynecol, 167: 1883-1887.
  • [67] Sommerfeld HJ, Meeker A, Piatyszek M, Bova S, Shay J, Coffey D (1996). Telomerase activity. A prevalent marker of malignant human prostate tissue. Cancer Res, 56: 218-222.
  • [68] Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G, de Lange T (2000). Control of human telomere length by TRF1 and TRF2. Mol Cell Biol, 20: 1659-1668.
  • [69] Sun D, Thompson B, Cathers BE, Salazar M, Kerwin SM, Trent JO, Jenkins TC, Neidle S, Hurley LH (1997). Inhibition of human telomerase by a G-quadruplex-interactive compound. J Med Chem, 40: 2113-2116.
  • [70] van Steensel B, Smogorzewska A, de Lange T (1998). TRF2 protects human telomeres from end-to-end fusion. Cell, 92: 402-413.
  • [71] van Steensel B, de Lange T (1997). Control of telomere length by the human telomeric protein TRF1. Nature, 385: 740-743.
  • [72] Vonderheide RH, Hahn WC, Schultze JL, et al., (1999). The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity, 10: 673-679.
  • [73] Wataru Y, Hidetoshi T, Eiji T, et al., (1998). Expression of telomerase catalytic compontent, telomerase reverse transcriptase, in human gastric carcinomas. Jpn J Cancer Res, 89: 1099-1103.
  • [74] Watson JD (1972). Origin of concatemeric T7 DNA. Nat New Biol, 239: 197-201.
  • [75] Wei Lixin, Wu Mengchao, Guo Yajun, et al., Detection of human telomerase activity by telomerase TRAP-ELISA assay. Chinese Journal of Cancer Research 1997; 9(4): 277-80.
  • [76] Wei Lixin, Guo Yajun, Wu Mengchao, et al., Detection of telomerase activity in human cells with telomeric repeat amplification protocol by silver staining. Med Cell PLA 1998; 13(2): 140-142.
  • [77] Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichsteiner S, Kim NW, Trager JB, et al., (1997). Reconstitution of human telomerase with the catalytic protein subunit hTRT. Nature Genet, 17: 498-502.
  • [78] Wright W, Piatyszek M, Rainey W, Byrd W, Shay J, (1996). Telomerase activity in human germline and embryonic tissues and cells. Dev Genet, 18: 173-179.
  • [79] Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, Yamamoto H, et al., (1996). Telomerase activity in normal human epithelial cells. Oncogene, 13: 433-439.
  • [80] Yokoyama Y, Takahashi Y, Shinohara A, et al., (1998). Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells. Cancer Res, 58: 5406-5410.
  • [81] Zhu XD, Kuster B, Mann M, Petrini JHJ, de Lange T (2000). Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 human telomere. Nature Genet, 25: 347-352.
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bwmeta1.element.psjd-048b23c3-c677-47a3-8e1a-470d7c057f53
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