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REVIEW

The role of telomeres and telomerase in the pathology of human cancer and aging

, , &
Pages 103-113 | Received 03 Jan 2006, Accepted 12 Jan 2006, Published online: 06 Jul 2009

References

  • Hayflick L., Moorhead P. S. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25: 585–621
  • Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37: 614–36
  • Muller H. J. The remaking of chromosomes. Collecting Net 1938; 13: 181–98
  • McClintock B. The stability of broken ends of chromosomes in Zea mays. Genetics 1941; 26: 234–82
  • McClintock B. The fusion of broken ends of chromosomes following nuclear fusion. Proc Natl Acad Sci USA 1942; 28: 458–63
  • Moyzis R. K., Buckingham J. M., Cram L. S., et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 1988; 85: 6622–6
  • Makarov V. L., Hirose Y., Langmore J. P. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 1997; 88: 657–66
  • Wright W. E., Tesmer V. M., Huffman K. E., et al. Normal human chromosomes have long G‐rich telomeric overhangs at one end. Genes Dev 1997; 11: 2801–9
  • Griffith J. D., Comeau L., Rosenfield S., et al. Mammalian telomeres end in a large duplex loop. Cell 1999; 97: 503–14
  • van Steensel B., de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature 1997; 385: 740–3
  • van Steensel B., Smogorzewska A., de Lange T. TRF2 Protects human telomeres from end‐to‐end fusions. Cell 1998; 92: 401–13
  • Stansel R. M., de Lange T., Griffith J. D. T‐loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J 2001; 20: 5532–40
  • Baumann P., Cech T. R. Pot1, the putative telomere end‐binding protein in fission yeast and humans. Science 2001; 292: 1171–5
  • Wei C., Price C. M. Cell cycle localization, dimerization, and binding domain architecture of the telomere protein cPot1. Mol Cell Biol 2004; 24: 2091–102
  • Colgin L. M., Baran K., Baumann P., et al. Human POT1 facilitates telomere elongation by telomerase. Curr Biol 2003; 13: 942–6
  • Loayza D., de Lange T. POT1 as a terminal transducer of TRF1 telomere length control. Nature 2003; 423: 1013–8
  • Kelleher C., Kurth I., Lingner J. Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro. Mol Cell Biol 2005; 25: 808–18
  • Zhou X. Z., Lu K. P. The Pin2/TRF1‐interacting protein PinX1 is a potent telomerase inhibitor. Cell 2001; 107: 347–59
  • Kim S. H., Kaminker P., Campisi J. TIN2, a new regulator of telomere length in human cells. (See comment.). Nat Genet 1999; 23: 405–12
  • Smith S., Giriat I., Schmitt A., et al. Tankyrase, a poly(ADP‐ribose) polymerase at human telomeres. (Comment.). Science 1998; 282: 1484–7
  • Kaminker P. G., Kim S‐H., Taylor R. D., et al. TANK2, a new TRF1‐associated poly(ADP‐ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem 2001; 276: 35891–9
  • Bianchi A., de Lange T. Ku binds telomeric DNA in vitro. J Biol Chem 1999; 274: 21223–7
  • Hsu H‐L., Gilley D., Galande S. A., et al. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev 2000; 14: 2807–12
  • Song K., Jung D., Jung Y., et al. Interaction of human Ku70 with TRF2. FEBS Letters 2000; 481: 81–5
  • Li B., Oestreich S., de Lange T. Identification of human Rap1: implications for telomere evolution. Cell 2000; 101: 471–83
  • Zhu X. D., Kuster B., Mann M., et al. Cell‐cycle‐regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres. Nat Genet 2000; 25: 347–52
  • Ford L. P., Wright W. E., Shay J. W. A model for heterogeneous nuclear ribonucleoproteins in telomere and telomerase regulation. Oncogene 2002; 21: 580–3
  • Zhu X‐D., 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; 12: 1489–98
  • Olovnikov A. M. Principle of marginotomy in template synthesis of polyneucleotides. Dokl Akad Nauk SSSR 1971; 201: 1496–9
  • Olovnikov A. M. A theory of marginotomy: The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 1973; 41: 181–90
  • Watson J. D. Origin of concatemeric T7 DNA. Nature New Biol 1972; 239: 197–201
  • Harley C. B., Futcher A. B., Greider C. W. Telomeres shorten during ageing of human fibroblasts. Nature 1990; 345: 458–60
  • Hastie N. D., Dempster M., Dunlop M. G., et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 1990; 346: 866–8
  • de Lange T., Shiue L., Myers R. M., et al. Structure and variability of human chromosome ends. Mol Cell Biol 1990; 10: 518–27
  • Lindsey J., McGill N. I., Lindsey L. A., et al. In vivo loss of telomeric repeats with age in humans. Mutat Res 1991; 256: 45–8
  • Allsopp R. C., Vaziri H., Patterson C., et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992; 89: 10114–8
  • Counter C. M., Avilion A. A., LeFeuvre C. E., et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J 1992; 11: 1921–9
  • Allsopp R. C., Harley C. B. Evidence for a critical telomere length in senescent human fibroblasts. Exp Cell Res 1995; 219: 130–6
  • Wright W. E., Piatyszek M. A., Rainey W. E., et al. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet 1996; 18: 173–9
  • Holt S. E., Wright W. E., Shay J. W. Multiple pathways for the regulation of telomerase activity. Eur J Cancer 1997; 33: 761–6
  • Norrback K‐F., Roos G. Telomeres and telomerase in normal and malignant haematopoietic cells. Eur J Cancer 1997; 33: 774–80
  • Greider C. W. Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci USA 1998; 95: 90–2
  • Harrington L. Does the reservoir for self‐renewal stem from the ends?. Oncogene 2004; 23: 7283–9
  • Greider C. W., Blackburn E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43: 405–13
  • Greider C. W. Telomere length regulation. Annu Rev Biochem 1996; 65: 337–65
  • Harrington L. Biochemical aspects of telomerase function. Cancer Lett 2003; 194: 139–54
  • Nakamura T. M., Morin G. B., Chapman K. B., et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997; 277: 955–9
  • Meyerson M., Counter C. M., Eaton E. N., et al. hEST2, the putative human telomerase catalytic subunit gene, Is up‐regulated in tumor cells and during immortalization. Cell 1997; 90: 785–95
  • Harrington L., Zhou W., McPhail T., et al. Human telomerase contains evolutionarily conserved catalytic and structural subunits. Genes Dev 1997; 11: 3109–15
  • Kilian A., Bowtell D., Abud H., et al. Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types. Hum Mol Genet 1997; 6: 2011–9
  • Feng J., Funk W. D., Wang S. S., et al. The RNA component of human telomerase. Science 1995; 269: 1236–41
  • Beattie T. L., Zhou W., Robinson M. O., et al. Reconstitution of human telomerase activity in vitro. Curr Biol 1998; 8: 177–80
  • Vaziri H., Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol 1998; 8: 279–82
  • Wen J., Cong Y., Bacchetti S. Reconstitution of wild‐type or mutant telomerase activity in telomerase‐negative immortal human cells. Hum Mol Genet 1998; 7: 1137–41
  • Bachand F., Autexier C. Functional reconstitution of human telomerase expressed in Saccharomyces cerevisiae. J Biol Chem 1999; 274: 38027–31
  • D'Adda Di Fagagna F., Reaper P. M., Clay‐Farrace L., et al. A DNA damage checkpoint response in telomere‐initiated senescence. Nature 2003; 426: 194–8
  • Takai H., Smogorzewska A., de Lange T. DNA damage foci at dysfunctional telomeres. Curr Biol 2003; 13: 1549–56
  • Bakkenist C. J., Drissi R., Wu J., et al. Disappearance of the telomere dysfunction‐induced stress response in fully senescent cells. Cancer Res 2004; 64: 3748–52
  • Karlseder J., Broccoli D., Dai Y., et al. p53‐ and ATM‐dependent apoptosis induced by telomeres lacking TRF2. Science 1999; 283: 1321–5
  • Karlseder J., Smogorzewska A., de Lange T. Senescence induced by altered telomere state, not telomere loss. Science 2002; 295: 2446–9
  • Herbig U., Jobling W. A., Chen B. P. C., et al. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21CIP1, but not p16INK4a. Mol Cell 2004; 14: 501–13
  • Ferreira M. G., Cooper J. P. The fission yeast Taz1 protein protects chromosomes from Ku‐dependent end‐to‐end fusions. Mol Cell 2001; 7: 55–63
  • Smogorzewska A., Karlseder J., Holtgreve‐Grez H., et al. DNA ligase IV‐dependent NHEJ of deprotected mammalian telomeres in G1 and G2. Curr Biol 2002; 12: 1635–44
  • Espejel S., Franco S., Rodríguez‐Perales S., et al. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J 2002; 21: 2207–19
  • Espejel S., Franco S., Sgura A., et al. Functional interaction between DNA‐PKcs and telomerase in telomere length maintenance. EMBO J 2002; 21: 6275–87
  • Mieczkowski P. A., Mieczkowska J. O., Dominska M., et al. Genetic regulation of telomere‐telomere fusions in the yeast Saccharomyces cerevisae. Proc Natl Acad Sci USA 2003; 100: 10854–9
  • Nautiyal S., DeRisi J. L., Blackburn E. H. The genome‐wide expression response to telomerase deletion in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 2002; 99: 9316–21
  • Webley K., Bond J. A., Jones C. J., et al. Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Mol Cell Biol 2000; 20: 2803–8
  • d'Adda di Fagagna F., Teo S‐H., Jackson S. P. Functional links between telomeres and proteins of the DNA‐damage response. Genes Dev 2004; 18: 1781–99
  • Cabuy E., Newton C., Joksic G., et al. Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines. Radiat Res 2005; 164: 53–62
  • Slijepcevic P. Is there a link between telomere maintenance and radiosensitivity?. Radiat Res 2004; 161: 82–6
  • Chin L., Artandi S. E., 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
  • Murnane J. P., Sabatier L. Chromosome rearrangements resulting from telomere dysfunction and their role in cancer. Bioessays 2004; 26: 1164–74
  • Maser R. S., DePinho R. A. Connecting chromosomes, crisis and cancer. Science 2002; 297: 565–9
  • Shay J. W., Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer 1997; 33: 787–91
  • Neumann A. A., Reddel R. R. Telomere maintenance and cancer – look, no telomerase. Nat Rev Cancer 2002; 2: 879–84
  • Kim N. W., Piatyszek M. A., Prowse K. R., et al. Specific association of human telomerase activity with immortal cells and cancer. (See comment.). Science 1994; 266: 2011–5
  • Clark G. M., Osborne C. K., Levitt D., et al. Telomerase activity and survival of patients with node‐positive breast cancer. J Natl Cancer Inst 1997; 89: 1874–81
  • Melissourgos N., Kastrinakis N. G., Davilas I., et al. Detection of human telomerase reverse transcriptase mRNA in urine of patients with bladder cancer: evaluation of an emerging tumor marker. Urology 2003; 62: 362–7
  • Domont J., Pawlik T. M., Boige V., et al. Catalytic subunit of human telomerase reverse transcriptase is an independent predictor of survival in patients undergoing curative resection of hepatic colorectal metastases: a multicenter analysis. J Clin Oncol 2005; 23: 3086–93
  • Fujita Y., Fujikane T., Fujiuchi S., et al. The diagnostic and prognostic relevance of human telomerase reverse transcriptase mRNA expression detected in situ in patients with nonsmall cell lung carcinoma. Cancer 2003; 98: 1008–13
  • Tatsumoto N., Hiyama E., Murakami Y., et al. High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer. Clin Cancer Res 2000; 6: 2696–701
  • Meeker A. K., Hicks J. L., Gabrielson E., et al. Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma. Am J Pathol 2004; 164: 925–35
  • Roos G., Nilsson P., Cajander S., et al. Telomerase activity in relation to p53 status and clinico‐pathological parameters in breast cancer. Int J Cancer 1998; 79: 343–8
  • Poremba C., Heine B., Diallo R., et al. Telomerase as a prognostic marker in breast cancer: high‐throughput tissue microarray analysis of hTERT and hTR. (See comment.). J Pathol 2002; 198: 181–9
  • Bieche I., Nogues C., Paradis V., et al. Quantitation of hTERT gene expression in sporadic breast tumors with a real‐time reverse transcription‐polymerase chain reaction assay. Clin Cancer Res 2000; 6: 452–9
  • Hiyama E., Saeki T., Hiyama K., et al. Telomerase activity as a marker of breast carcinoma in fine‐needle aspirated samples. Cancer Cytopathology 2000; 90: 235–8
  • Wisman G. B. A., Knol A. J., Helder M. N., et al. Telomerase in relation to clinicopathologic prognostic factors and survival in cervical cancer. Int J Cancer 2001; 91: 658–64
  • Jarboe E. A., Thompson L. C., Heinz D., et al. Telomerase and human papillomavirus as diagnostic adjuncts for cervical dysplasia and carcinoma. Hum Pathol 2004; 35: 396–402
  • Marchetti A., Bertacca G., Buttitta F., et al. Telomerase activity as a prognostic indicator in stage I non‐small cell lung cancer. Clin Cancer Res 1999; 5: 2077–81
  • Taga S., Osaki T., Ohgami A., et al. Prognostic impact of telomerase activity in non‐small cell lung cancers. Ann Surg 1999; 230: 715–20
  • Wang L., Soria J‐C., Kemp B. L., et al. hTERT expression is a prognostic factor of survival in patients with stage I non‐small cell lung cancer. Clin Cancer Res 2002; 8: 2883–9
  • Miracco C., Pacenti L., Santopietro R., et al. Evaluation of telomerase activity in cutaneous melanocytic proliferations. Hum Pathol 2000; 31: 1018–21
  • Glaessl A., Bosserhoff A. K., Buettner R., et al. Increase in telomerase activity during progression of melanocytic cells from melanocytic naevi to malignant melanomas. Arch Dermatol Res 1999; 291: 81–7
  • Ramirez R. D., D'Atri S., Pagani E., et al. Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma. Neoplasia 1999; 1: 42–9
  • Miracco C., Margherita De Santi M., Schurfeld K., et al. Quantitative in situ evaluation of telomeres in fluorescence in situ hybridization‐processed sections of cutaneous melanocytic lesions and correlation with telomerase activity. Br J Dermatol 2002; 146: 399–408
  • Wullich B., Rohde V., Oehlenschlager B., et al. Focal intratumoral heterogeneity for telomerase activity in human prostate cancer. J Urol 1999; 161: 1997–2001
  • Lin Y., Uemura H., Fujinami K., et al. Telomerase activity in primary prostate cancer. J Urol 1997; 157: 1161–5
  • Kamradt J., Drosse C., Kalkbrenner S., et al. Telomerase activity and telomerase subunit gene expression levels are not related in prostate cancer: a real‐time quantification and in situ hybridization study. Lab Invest 2003; 83: 623–33
  • Bettendorf O., Heine B., Kneif S., et al. Expression‐patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer. Prostate 2003; 55: 99–104
  • Iczkowski K. A., Pantazis C. G., McGregor D. H., et al. Telomerase reverse transcriptase subunit immunoreactivity. Cancer 2002; 95: 2487–93
  • Latil A., Vidaud D., Valéri A., et al. htert expression correlates with MYC over‐expression in human prostate cancer. Int J Cancer 2000; 89: 172–6
  • Cakir C., Gulluoglu M., Yilmazbayhan D. Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations. Pathology 2006; 38: 10–15
  • Serrano M., Blasco M. A. Putting the stress on senescence. Curr Opin Cell Biol 2001; 13: 748–53
  • Wright W. E., Shay J. W. Cellular senescence as a tumor‐protection mechanism: the essential role of counting. Curr Opin Genet Dev 2001; 11: 98–103
  • Krtolica A., Campisi J. Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol 2002; 34: 1401–14
  • Takubo K., Izumiyama‐Shimomura N., Honma N., et al. Telomere lengths are characteristic in each human individual. Exp Gerontol 2002; 37: 523–31
  • Baird D. M., Kipling D. The extent and significance of telomere loss with age. Ann NY Acad Sci 2004; 1019: 265–8
  • Frenck R. W., Jr., Blackburn E. H., Shannon K. M. The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci USA 1998; 95: 5607–10
  • Oshima J. The Werner syndrome protein: an update. Bioessays 2000; 22: 894–901
  • Bohr V. A., Cooper M., Orren D., et al. Werner syndrome protein: biochemical properties and functional interactions. Exp Gerontol 2000; 35: 695–702
  • Ellis N. A., Groden J., Ye T‐Z., et al. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 1995; 83: 655–66
  • Mohaghegh P., Hickson I. D. DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum Mol Genet 2001; 10: 741–6
  • German J. Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine 1993; 72: 393–406
  • Opresko P. L., von Kobbe C., Laine J‐P., et al. Telomere‐binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 2002; 277: 41110–9
  • Yankiwski V., Marciniak R. A., Guarente L., et al. Nuclear structure in normal and Bloom syndrome cells. Proc Natl Acad Sci USA 2000; 97: 5214–9
  • Opresko P. L., Cheng W‐H., 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: 791–802
  • Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000; 110: 768–79
  • Heiss N. S., Knight S. W., Vulliamy T. J., et al. X‐linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 1998; 19: 32–8
  • Mitchell J. R., Wood E., Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999; 402: 551–5
  • Bachellerie J‐P., Cavaille J., Huttenhofer A. The expanding snoRNA world. Biochimie 2002; 84: 775–90
  • Kiss T. Small nucleolar RNA‐guided post‐transcriptional modification of cellular RNAs. EMBO J 2001; 20: 3617–22
  • Mitchell J. R., Cheng J., Collins K. A box H/ACA small nucleolar RNA‐like domain at the human telomerase RNA 3′ end. Mol Cell Biol 1999; 19: 567–76
  • Chen J‐L., Blasco M. A., Greider C. W. Secondary structure of vertebrate telomerase RNA. Cell 2000; 100: 503–14
  • Antal M., Boros E., Solymosy F., et al. Analysis of the structure of human telomerase RNA in vivo. Nucl Acids Res 2002; 30: 912–20
  • Fu D., Collins K. Distinct biogenesis pathways for human telomerase RNA and H/ACA small nucleolar RNAs. Mol Cell 2003; 11: 1361–72
  • Narayanan A., Lukowiak A., Jady B. E., et al. Nucleolar localization signals of box H/ACA small nucleolar RNAs. EMBO J 1999; 18: 5120–30
  • Lukowiak A. A., Narayanan A., Li Z. H., et al. The snoRNA domain of vertebrate telomerase RNA functions to localize the RNA within the nucleus. RNA 2001; 7: 1833–44
  • Dragon F., Pogacic V., Filipowicz W. In vitro assembly of human H/ACA small nucleolar RNPs reveals unique features of U17 and telomerase RNAs. Mol Cell Biol 2000; 20: 3037–48
  • Pogacic V., Dragon F., Filipowicz W. Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Mol Cell Biol 2000; 20: 9028–40
  • Dez C., Henras A., Faucon B., et al. Stable expression in yeast of the mature form of human telomerase RNA depends on its association with the box H/ACA small nucleolar RNP proteins Cbf5p, Nhp2p and Nop10p. Nucleic Acids Res 2001; 29: 598–603
  • Wong J. M. Y., Kyasa M. J., Hutchins L., et al. Telomerase RNA deficiency in peripheral blood mononuclear cells in X‐linked dyskeratosis congenita. Hum Genet 2004; 115: 448–55
  • Montanaro L., Tazzari P. L., Derenzini M. Enhanced telomere shortening in transformed lymphoblasts from patients with X linked dyskeratosis. J Clin Pathol 2003; 56: 583–6
  • Vulliamy T. J., Knight S. W., Mason P. J., et al. Very short telomeres in the peripheral blood of patients with X‐linked and autosomal dyskeratosis congenita. Blood Cells Mol Dis 2001; 27: 353–7
  • Vulliamy T., Marrone A., Goldman F., et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001; 413: 432–5
  • Vulliamy T., Marrone A., Dokal I., et al. Association between aplastic anaemia and mutations in telomerase RNA. Lancet 2002; 359: 2168–70
  • Yamaguchi H., Baerlocher G. M., Lansdorp P. M., et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood 2003; 102: 916–8
  • Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 2005; 120: 513–22
  • Mokbel K., Parris C. N., Radbourne R., et al. Telomerase activity and prognosis in breast cancer. Eur J Surg Oncol 1999; 25: 269–72
  • Hoos A., Hepp H. H., Kaul S., et al. Telomerase activity correlates with tumor aggressiveness and reflects therapy effect in breast cancer. Int J Cancer 1998; 79: 8–12
  • Mokbel K., Ghilchik M., Williams G., et al. The association between telomerase activity and hormone receptor status and p53 expression in breast cancer. Int J Surg Invest 2000; 1: 509–16
  • Swellam M., Ismail M., Eissa S., et al. Emerging role of p53, bcl‐2 and telomerase activity in Egyptian breast cancer patients. IUBMB Life 2004; 56: 483–90
  • Umbricht C. B., Sherman M. E., Dome J., et al. Telomerase activity in ductal carcinoma in situ and invasive breast cancer. Oncogene 1999; 18: 3407–14
  • Kassim S. K., Fawzy H., El Rassad M. M., et al. Telomerase activity, and tissue polypeptide specific antigen (TPS) in Egyptian breast cancer patients. Clin Biochem 2001; 34: 499–504
  • Mokbel K. M., Parris C. N., Ghilchik M., et al. Telomerase activity and lymphovascular invasion in breast cancer. Eur J Surg Oncol 2000; 26: 30–3
  • Yang W., Xu L., Zhang T. Telomerase activity in breast carcinoma. (Chinese.). Zhonghua Zhong Liu Za Zhi 1999; 21: 278–80
  • Hiyama E., Gollahon L., Kataoka T., et al. Telomerase activity in human breast tumors. J Natl Cancer Inst 1996; 88: 116–22
  • Kimura M., Koida T., Yanagita Y. A study on telomerase activity and prognosis in breast cancer. Med Oncol 2003; 20: 117–26
  • Simickova M., Nekulova M., Pecen L., et al. Quantitative determination of telomerase activity in breast cancer and benign breast diseases. Neoplasma 2001; 48: 267–73
  • Wu S., Liu Z., Sun H. Telomerase activity in infiltration ductal carcinoma of breast. (Chinese.). Zhonghua Yi Xue Za Zhi 1998; 78: 515–6
  • Bednarek A. K., Sahin A., Brenner A. J., et al. Analysis of telomerase activity levels in breast cancer: positive detection at the in situ breast carcinoma stage. Clin Cancer Res 1997; 3: 11–6
  • Sugino T., Yoshida K., Bolodeoku J., et al. Telomerase activity in human breast cancer and benign breast lesions: diagnostic applications in clinical specimens, including fine needle aspirates. Int J Cancer 1996; 69: 301–6
  • Tsao J., Zhao Y., Lukas J., et al. Telomerase activity in normal and neoplastic breast. Clin Cancer Res 1997; 3: 627–31
  • Carey L. A., Kim N. W., Goodman S., et al. Telomerase activity and prognosis in primary breast cancers. J Clin Oncol 1999; 17: 3075–81
  • Kirkpatrick K. L., Ogunkolade W., Elkak A. E., 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
  • Griffith J. K., Bryant J. E., Fordyce C. A., et al. Reduced telomere DNA content is correlated with genomic instability and metastasis in invasive human breast carcinoma. Breast Cancer Res Treat 1999; 54: 59–64
  • Rogalla P., Rohen C., Bonk U., et al. Telomeric repeat fragment lengths are not correlated to histological grading in 85 breast cancers. Cancer Lett 1996; 106: 155–61
  • Nair P., Jayaprakash P. G., Nair M. K., et al. Telomerase, p53 and human papillomavirus infection in the uterine cervix. Acta Oncol 2000; 39: 65–70
  • Riethdorf S., Riethdorf L., Schulz G., et al. Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol 2001; 20: 177–85
  • Wang S. Z., Sun J. H., Zhang W., et al. Telomerase activity in cervical intraepithelial neoplasia. Chin Med J (Engl) 2004; 117: 202–6
  • Wisman G. B., Hollema H., de Jong S., et al. Telomerase activity as a biomarker for (pre)neoplastic cervical disease in scrapings and frozen sections from patients with abnormal cervical smear. J Clin Oncol 1998; 16: 2238–45
  • Leng B., Bian M., Sun A., et al. Telomerase activity in cervical carcinoma and cervical intraepithelial neoplasia and its correlation to classification of koilocytosis. (Chinese.). Zhonghua Yi Xue Za Zhi 2002; 82: 262–6
  • Snijders P. J., van Duin M., Walboomers J. M., et al. Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high‐risk human papillomavirus DNA. Cancer Res 1998; 58: 3812–8
  • Kyo S., Takakura M., Tanaka M., et al. Telomerase activity in cervical cancer is quantitatively distinct from that in its precursor lesions. Int J Cancer 1998; 79: 66–70
  • Nagai N., Oshita T., Murakami J., et al. Semiquantitative analysis of telomerase activity in cervical cancer and precancerous lesions. Oncol Rep 1999; 6: 325–8
  • Qiao Y., Zhang M., Shi H. Telomerase activity in cervical cancer and its precursor lesion. (Chinese.). Zhonghua Fu Chan Ke Za Zhi 2001; 36: 483–5
  • Zhang D. K., Ngan H. Y. S., Cheng R. Y. S., et al. Clinical significance of telomerase activation and telomeric restriction fragment (TRF) in cervical cancer. Eur J Cancer 1999; 35: 154–60
  • Zheng P‐S., Iwasaka T., Yokoyama M., et al. Telomerase activation in in vitro and in vivo cervical carcinogenesis. Gynecol Oncol 1997; 66: 222–6
  • Ault K. A., Allen H. K., Phillips S. L., et al. Telomerase activity as a potential diagnostic marker for triage of abnormal Pap smears. J Low Genit Tract Dis 2005; 9: 93–9
  • Iwasaka T., Zheng P. S., Yokoyama M., et al. Telomerase activation in cervical neoplasia. Obstet Gynecol 1998; 91: 260–2
  • Reesink‐Peters N., Helder M. N., Wisman G. B., et al. Detection of telomerase, its components, and human papillomavirus in cervical scrapings as a tool for triage in women with cervical dysplasia. J Clin Pathol 2003; 56: 31–5
  • Ngan H. Y., Cheung A. N., Liu S. S., et al. Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological cervical cancer screening. Tumour Biol 2002; 23: 87–92
  • Wisman G. B. A., De Jong S., Meersma G. J., et al. Telomerase in (pre)neoplastic cervical disease. Hum Pathol 2000; 31: 1304–12
  • Widschwendter A., Muller H. M., Hubalek M. M., et al. Methylation status and expression of human telomerase reverse transcriptase in ovarian and cervical cancer. Gynecol Oncol 2004; 93: 407–16
  • Takakura M., Kyo S., Kanaya T., et al. Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res 1998; 58: 1558–61
  • Zhang A., Wang J., Zheng B., et al. Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix. Oncogene 2004; 23: 7441–7
  • Fujita M., Tomita S., Fukui H., et al. Semi‐quantitative procedure for telomeric repeat amplification protocol (TRAP) assay in colorectal carcinomas. J Exp Clin Cancer Res 1999; 18: 119–24
  • Okayasu I., Mitomi H., Yamashita K., et al. Telomerase activity significantly correlates with cell differentiation, proliferation and lymph node metastasis in colorectal carcinomas. J Cancer Res Clin Oncol 1998; 124: 444–9
  • Naito Y., Takagi T., Handa O., et al. Telomerase activity and expression of telomerase RNA component and catalytic subunits in precancerous and cancerous colorectal lesions. Tumour Biol 2001; 22: 374–82
  • Kawanishi‐Tabata R., Lopez F., Fratantonio S., et al. Telomerase activity in stage II colorectal carcinoma. Cancer 2002; 95: 1834–9
  • Ohki S., Satoh H., Watanabe F., et al. Telomerase activity in colorectal cancer–a semi‐quantitative procedure. (Japanese.). Gan To Kagaku Ryoho 1998; 25: 469–74
  • Shoji Y., Yoshinaga K., Inoue A., et al. Quantification of telomerase activity in sporadic colorectal carcinoma. Cancer 2000; 88: 1304–9
  • Malaska J., Kunicka Z., Borsky M., et al. Telomerase as a diagnostic and predictive marker in colorectal carcinoma. Neoplasma 2004; 51: 90–6
  • Engelhardt M., Drullinsky P., Guillem J., et al. Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin Cancer Res 1997; 3: 1931–41
  • Lukman K., Maskoen A. M., Achmad T. H., et al. Telomerase activity in different clinical staging of colorectal adenocarcinoma. (Japanese.). Gan To Kagaku Ryoho 2000; 27: 491–7
  • Brown T., Aldous W., Lance R., et al. The association between telomerase, p53, and clinical staging in colorectal cancer. Am J Surg 1998; 175: 364–6
  • Fang D‐C., Young J., Luo Y‐H., et al. Detection of telomerase activity in biopsy samples of colorectal cancer. J Gastroenterol Hepatol 1999; 14: 328–32
  • Abe N., Watanabe T., Nakashima M., et al. Quantitative analysis of telomerase activity: a potential diagnostic tool for colorectal carcinoma. Hepatogastroenterology 2001; 48: 692–5
  • Iida A., Yamaguchi A., Hirose K. Telomerase activity in colorectal cancer and its relationship to bcl‐2 expression. J Surg Oncol 2000; 73: 219–23
  • Luo C., Zhao D., Qu J. Telomerase activity in stool of patients with colorectal cancer. (Chinese.). Zhonghua Wai Ke Za Zhi 2001; 39: 580–2
  • Ishibashi K., Hirose K., Kato H., et al. Determining the telomerase activity of exfoliated cells in intestinal lavage solution to detect colorectal carcinoma. Anticancer Res 1999; 19: 2831–6
  • Gertler R., Rosenberg R., Stricker D., et al. Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma. Cancer 2002; 95: 2103–11
  • Wei R., Younes M. Immunohistochemical detection of telomerase reverse transcriptase in colorectal adenocarcinoma and benign colonic mucosa. Hum Pathol 2002; 33: 693–6
  • Kim H. R., Kim Y. J., Kim H. J., et al. Telomere length changes in colorectal cancers and polyps. J Korean Med Sci 2002; 17: 360–5
  • Gertler R., Rosenberg R., Stricker D., et al. Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol 2004; 22: 1807–14
  • Takagi S., Kinouchi Y., Hiwatashi N., et al. Telomere shortening and the clinicopathologic characteristics of human colorectal carcinomas. Cancer 1999; 86: 1431–6
  • Hara H., Yamashita K., Shinada J., et al. Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non‐small cell lung cancer. Lung Cancer 2001; 34: 219–26
  • Gonzalez‐Quevedo R., Iniesta P., Moran A., et al. Cooperative role of telomerase activity and p16 expression in the prognosis of non‐small‐cell lung cancer. J Clin Oncol 2002; 20: 254–62
  • Fujiwara M., Okayasu I., Takemura T., et al. Telomerase activity significantly correlates with chromosome alterations, cell differentiation, and proliferation in lung adenocarcinomas. Mod Pathol 2000; 13: 723–9
  • Liu H., Zhang W., Cai C., et al. Telomerase activity in human non‐small cell lung cancer (NSCLC). (Chinese.). Zhonghua Bing Li Xue Za Zhi 2000; 29: 89–91
  • Kumaki F., Kawai T., Hiroi S., et al. Telomerase activity and expression of human telomerase RNA component and human telomerase reverse transcriptase in lung carcinomas. Hum Pathol 2001; 32: 188–95
  • Ohmura Y., Aoe M., Andou A., et al. Telomerase activity and bcl‐2 expression in non‐small cell lung cancer. Clin Cancer Res 2000; 6: 2980–7
  • Albanell J., Lonardo F., Rusch V., et al. High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage. J Natl Cancer Inst 1997; 89: 1609–15
  • Hsu C‐P., Miaw J., Hsia J‐Y., et al. Concordant expression of the telomerase‐associated genes in non‐small cell lung cancer. Eur J Surg Oncol 2003; 29: 594–9
  • Wang J., Liu X., Jiang W., et al. Telomerase activity and expression of the telomerase catalytic subunit gene in non‐small cell lung cancer: correlation with decreased apoptosis and clinical prognosis. Chin Med J (Engl) 2000; 113: 985–90
  • Lantuejoul S., Soria J. C., Moro‐Sibilot D., et al. Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours. Br J Cancer 2004; 90: 1222–9
  • Marchetti A., Pellegrini C., Buttitta F., et al. Prediction of survival in stage I lung carcinoma patients by telomerase function evaluation. Lab Invest 2002; 82: 729–36
  • Wu T. C., Lin P., Hsu C. P., et al. Loss of telomerase activity may be a potential favorable prognostic marker in lung carcinomas. Lung Cancer 2003; 41: 163–9
  • Chen Q., He J., Yi H. Study on telomerase activity and its clinical value in human non small cell lung cancer. (Chinese.). Hunan Yi Ke Da Xue Xue Bao 2001; 26: 221–2
  • He M., Xu S., Wang X. Telomerase activity in lung cancer and adjacent peritumoral tissues determined by TRAP‐SYBR green assay. (Chinese.). Zhonghua Yu Fang Yi Xue Za Zhi 2001; 35: 301–4
  • Arai T., Yasuda Y., Takaya T., et al. Application of telomerase activity for screening of primary lung cancer in broncho‐alveolar lavage fluid. Oncol Rep 1998; 5: 405–8
  • Dikmen E., Kara M., Dikmen G., et al. Detection of telomerase activity in bronchial lavage as an adjunct to cytological diagnosis in lung cancer. Eur J Cardiothorac Surg 2003; 23: 194–200
  • Xinarianos G., Scott F. M., Liloglou T., et al. Evaluation of telomerase activity in bronchial lavage as a potential diagnostic marker for malignant lung disease. Lung Cancer 2000; 28: 37–42
  • Sen S., Reddy V. G., Guleria R., et al. Telomerase–a potential molecular marker of lung and cervical cancer. Clin Chem Lab Med 2002; 40: 994–1001
  • Yahata N., Ohyashiki K., Ohyashiki J. H., et al. Telomerase activity in lung cancer cells obtained from bronchial washings. J Natl Cancer Inst 1998; 90: 684–90
  • Freitag L., Litterst P., Obertrifter B., et al. Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas. Pneumologie 2000; 54: 480–5
  • Toomey D., Smyth G., Condron C., et al. Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features. Cancer 2001; 92: 2648–57
  • Geng Z., Zhang D., Liu Y. Expression of telomerase hTERT in human non‐small cell lung cancer and its correlation with c‐myc gene. Chin Med J (Engl) 2003; 116: 1467–70
  • Arinaga M., Shimizu S., Gotoh K., et al. Expression of human telomerase subunit genes in primary lung cancer and its clinical significance. Ann Thorac Surg 2000; 70: 401–5
  • Ma G., Gao J. S., Tong M., et al. Detection of telomerase hTERT gene expression of exfoliated cell in broncho‐alveolar lavage fluid. Ai Zheng 2002; 21: 533–5
  • Shirotani Y., Hiyama K., Ishioka S., et al. Alteration in length of telomeric repeats in lung cancer. Lung Cancer 1994; 11: 29–41
  • Miracco C., Pacenti L., Santopietro R., et al. Detection of telomerase activity and correlation with mitotic and apoptotic indices, Ki‐67 and expression of cyclins D1 and A in cutaneous melanoma. Int J Cancer 2000; 88: 411–6
  • Rudolph P., Schubert C., Tamm S., et al. Telomerase activity in melanocytic lesions: A potential marker of tumor biology. Am J Pathol 2000; 156: 1425–32
  • Lin Y., Uemura H., Fujinami K., et al. Detection of telomerase activity in prostate needle‐biopsy samples. Prostate 1998; 36: 121–8
  • Zhang W., Kapusta L., Slingerland J., et al. Telomerase activity in prostate cancer, prostatic intraepithelial neoplasia, and benign prostatic epithelium. Cancer Res 1998; 58: 619–21
  • Wang Z., Ramin S. A., Tsai C., et al. Evaluation of PCR‐ELISA for determination of telomerase activity in prostate needle biopsy and prostatic fluid specimens,. Urol Oncol 2002; 7: 199–205
  • Meid F. H., Gygi C. M., Leisinger H. J., et al. The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage. J Urol 2001; 165: 1802–5
  • Donaldson L., Fordyce C., Gilliland F., et al. Association between outcome and telomere DNA content in prostate cancer. J Urol 1999; 162: 1788–92
  • Vukovic B., Park P. C., Al‐Maghrabi J., et al. Evidence of multifocality of telomere erosion in high‐grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma. Oncogene 2003; 22: 1978–87
  • Lin Y., Miyamoto H., Fujinami K., et al. Telomerase activity in human bladder cancer. Clin Cancer Res 1996; 2: 929–32
  • Longchampt E., Lebret T., Molinie V., et al. Detection of telomerase status by semiquantitative and in situ assays, and by real‐time reverse transcription‐polymerase chain reaction (telomerase reverse transcriptase) assay in bladder carcinomas. BJU Int 2003; 91: 567–72
  • Yokota K., Kanda K., Inoue Y., et al. Semi‐quantitative analysis of telomerase activity in exfoliated human urothelial cells and bladder transitional cell carcinoma. (See comment.). Br J Urol 1998; 82: 727–32
  • Wu W. J., Liu L. T., Huang C. H., et al. Telomerase activity in human bladder tumors and bladder washing specimens. Kaohsiung J Med Sci 2001; 17: 602–9
  • Kyo S., Kunimi K., Uchibayashi T., et al. Telomerase activity in human urothelial tumors. (See comment.). Am J Clin Pathol 1997; 107: 555–60
  • Gelmini S., Crisci A., Salvadori B., et al. Comparison of telomerase activity in bladder carcinoma and exfoliated cells collected in urine and bladder washings, using a quantitative assay. Clin Cancer Res 2000; 6: 2771–6
  • Arias Funez F., Fernandez Fernandez E., Escudero Barrilero A., et al. Telomerase activity as marker of superficial tumor of the bladder. Arch Esp Urol 2000; 53: 231–6
  • Bhuiyan J., Akhter J., O'Kane D. J. Performance characteristics of multiple urinary tumor markers and sample collection techniques in the detection of transitional cell carcinoma of the bladder. Clinica Chimica Acta 2003; 331: 69–77
  • Cheng C. W., Chueh S. C., Chern H. D. Diagnosis of bladder cancer using telomerase activity in voided urine. J Formos Med Assoc 2000; 99: 920–5
  • Eissa S., Labib R. A., Mourad M. S., et al. Comparison of telomerase activity and matrix metalloproteinase‐9 in voided urine and bladder wash samples as a useful diagnostic tool for bladder cancer. Eur Urol 2003; 44: 687–94
  • Kavaler E., Landman J., Chang Y., et al. Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity. Cancer 1998; 82: 708–14
  • Dalbagni G., Han W., Zhang Z. F., et al. Evaluation of the telomeric repeat amplification protocol (TRAP) assay for telomerase as a diagnostic modality in recurrent bladder cancer. Clin Cancer Res 1997; 3: 1593–8
  • De Kok J. B., Schalken J. A., Aalders T. W., et al. Quantitative measurement of telomerase reverse transcriptase (hTERT) mRNA in urothelial cell carcinomas. Int J Cancer 2000; 87: 217–20
  • Suzuki T., Suzuki Y., Fujioka T. Expression of the catalytic subunit associated with telomerase gene in human urinary bladder cancer. [see comment]. J Urol 1999; 162: 2217–20
  • Kamata S., Kageyama Y., Yonese J., et al. Significant telomere reduction in human superficial transitional cell carcinoma. Br J Urol 1996; 78: 704–8

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