The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Abstract
Synthesis of DNA at chromosome ends by telomerase may be necessary for indefinite proliferation of human cells. A highly sensitive assay for measuring telomerase activity was developed. In cultured cells representing 18 different human tissues, 98 of 100 immortal and none of 22 mortal populations were positive for telomerase. Similarly, 90 of 101 biopsies representing 12 human tumor types and none of 50 normal somatic tissues were positive. Normal ovaries and testes were positive, but benign tumors such as fibroids were negative. Thus, telomerase appears to be stringently repressed in normal human somatic tissues but reactivated in cancer, where immortal cells are likely required to maintain tumor growth.
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In the citing paper
“Furthermore, although most human cancers (~90%) escape telomere crisis by activating telomerase56, a significant minority of cancers use an alternative telomere maintenance system, referred to as alternative lengthening of telomeres (ALT)161.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [56]
In the citing paper
“The notion that telomere function may indeed be required for immortalization is supported by the frequent activation of telomerase or ALT in human cancers (Kim et al. 1994; Bryan et al. 1995”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Kim et al. 1994
In the citing paper
“Telomerase activation is observed in approximately 90% of human cancers, irrespective of tumor type, while most normal tissues contain inactivated telomerase.(1)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [1]
In the citing paper
“This idea is consistent with the fact that telomerase activity is upregulated in most human cancers, which probably contributes to sustaining their immortality7.”
From The telomere syndromes (2012) · cites this paper as [7]
In the citing paper
“Virally transformed human cells that eliminate p53 and/or pRB function can escape crisis at very low frequencies, and invariably adopt telomere-maintenance programs: 80-90% of human tumors possess some telomerase activity, while the remainder maintain telomeres via a recombination-mediated process termed ALT (for Alternative Lengthening of Telomeres)37-40.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [38]
In the citing paper
“Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“In cancer cells, the reactivation of telomerase is thought to stabilize telomere length, thereby compensating for the cell division-related telomere erosion and providing unlimited proliferative capacity to malignant cells (Counter et al., 1992;Kim et al., 1994).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase activity has been demonstrated in immortalized cell lines and in 80±90% of human cancer specimens representing a range of cancer types (Counter et al., 1994;Kim et al., 1994;Shay and Bacchetti, 1997)”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase activity has been found in almost all human tumors but not in adjacent normal cells (3, 4).”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [3]
In the citing paper
“Over the last decade it has become clear that most human cancers activate telomerase at some point during tumorigenesis, while this activity is largely absent in most normal tissues 70, 71 .”
From The common biology of cancer and ageing (2007) · cites this paper as [70]
Citations
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Self-citationStructure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M. A. C., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L., & Wu, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.18.6622 · Cited by 2,326
Telomere length predicts replicative capacity of human fibroblasts.
Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10114 · Cited by 2,200
Self-citationCounter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096
Self-citationOlovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis
Greider, C. W., & Blackburn, E. H. (1989) · Nature · doi:10.1038/337331a0 · Cited by 1,643
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495
Flagged first, then by citations
Research works printed but not linked: 2
- GARNICK, M.B., THE DILEMMAS OF PROSTATE-CANCER, SCIENTIFIC AMERICAN 270: 72 (1994).
- WATSON, J. D., NATURE-NEW BIOLOGY 239: 197 (1972).
Cited by
Sorted by citations
Items 101–200 of 1,043
Vonderheide, R. H., Hahn, W. C., Schultze, J. L., & Nadler, L. M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80066-7 · Cited by 579
Comparative biology of mouse versus human cells: modelling human cancer in mice
Rangarajan, A., & Weinberg, R. A. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1235 · Cited by 579
“, whereas many adult human somatic cells lack readily detectable levels of this enzyme activit”
BackgroundThe transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer
Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. D., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., et al. (2015) · Science · doi:10.1126/science.aab0015 · Cited by 566
Connecting Chromosomes, Crisis, and Cancer
Maser, R. S., & DePinho, R. A. (2002) · Science · doi:10.1126/science.297.5581.565 · Cited by 561
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553
Dai, J., Carver, M., Punchihewa, C., Jones, R. A., & Yang, D. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm522 · Cited by 559
“Telomerase has been shown to be activated in 80–85% of human cancer cells (17), and has been suggested to play a key role in maintaining the malignant phenotype by stabilizing telomere length and integrity (18).”
BackgroundTERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas
Melo, M., da Rocha, A. G., Vinagre, J., Batısta, R., Peixoto, J., Tavares, C., Celestino, R., de Almeida, A. P., Salgado, C., Eloy, C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3734 · Cited by 561
“Telomerase activation is known to be a hallmark of cancer (1), being detected in up to 80% of malignant tumors (2, 3).”
BackgroundNeidle, S. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07463.x · Cited by 557
Vascular Cell Senescence: Contribution to Atherosclerosis
Minamino, T., & Komuro, I. (2007) · Circulation Research · doi:10.1161/01.res.0000256837.40544.4a · Cited by 542
Teixeira, M. T., Arneric, M., Sperisen, P., & Lingner, J. (2004) · Cell · doi:10.1016/s0092-8674(04)00334-4 · Cited by 526
Herbert, B.-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., & Corey, D. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14276 · Cited by 539
Self-citationHuman telomeric G‐quadruplex: structures of DNA and RNA sequences
Phan, A. T. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07464.x · Cited by 560
G-quadruplexes: a promising target for cancer therapy
Kosiol, N., Juranek, S., Brossart, P., Heine, A., & Paeschke, K. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01328-4 · Cited by 561
“omerase activity is upregulated, which allows the cell to replicate without telomere shortening [56].”
BackgroundFunctional requirement of p23 and Hsp90 in telomerase complexesPreprint
Holt, S. E., Aisner, D. L., Baur, J. A., Tesmer, V. M., Dy, M., Ouellette, M., Trager, J. B., Morin, G. B., Toft, D. O., Shay, J. W., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.817 · Cited by 543
“HT1080, a human fibrosarcoma cell line, is immortal and expresses active telomerase (Kim et al. 1994).”
BackgroundSelf-citationThe biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538
TIN2, a new regulator of telomere length in human cells
Kim, S.-H., Kaminker, P., & Campisi, J. (1999) · Nature Genetics · doi:10.1038/70508 · Cited by 525
“Many tumour cells express telomerase, but maintain TRFs that are longer or shorter than 5–7 kb (ref”
BackgroundInvited Review: Theories of aging
Weinert, B. T., & Timiras, P. S. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00288.2003 · Cited by 546
“Additionally, all cancer cells activate telomerase or an alternate pathway of telomere extension to avoid replicative senescence (41, 73).”
Yan, H., Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H. S., Gallia, G. L., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou206.18 · Cited by 531
Telomere dysfunction and evolution of intestinal carcinoma in mice and humans
Rudolph, K. L., Millard, M., Bosenberg, M. W., & DePinho, R. A. (2001) · Nature Genetics · doi:10.1038/88871 · Cited by 527
“gif" NDATA ITEM> ]> Telomerase activation is a common feature of advanced human cancer”
Role of telomeres and telomerase in cancer
Shay, J. W., & Wright, W. E. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.10.001 · Cited by 523
“However, one of the hallmarks of advanced malignancies is continuous cell growth and this almost universally correlates with the reactivation of telomerase [7].”
BackgroundSelf-citationPhan, A. T., Kuryavyi, V., Luu, K. N., & Patel, D. J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm706 · Cited by 520
“G-quadruplexes formed by human telomere sequences are promising anticancer targets (12–16), because formation of such structures inhibits the activity of telomerase (17–19), an enzyme (20) that is required for the proliferation of 80%–85% of cancer cells (21).”
BackgroundShay, J. W. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.677 · Cited by 525
“Most human cancers have short telomeres and express high levels of telomerase, whereas in most normal somatic tissues telomerase is absent (35,36).”
BackgroundSelf-citationA Box H/ACA Small Nucleolar RNA-Like Domain at the Human Telomerase RNA 3′ End
Mitchell, J. R., Cheng, J., & Collins, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.567 · Cited by 510
“Telomerase activity was detected by the PCR-based telomere repeat amplification protocol (TRAP [27]) with minor alterations: extension was performed at 30°C for 1 h with 5 ml of extract diluted in buffer Z in a final volume of 47.”
MethodTelomestatin, a Novel Telomerase Inhibitor from Streptomyces anulatus
Shin‐ya, K., Wierzba, K., Matsuo, K., Ohtani, T., Yamada, Y., Furihata, K., Hayakawa, Y., & Seto, H. (2001) · Journal of the American Chemical Society · doi:10.1021/ja005780q · Cited by 524
Estrogen activates telomerase.
Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., FUJIMOTO, K., Nishio, Y., Orimo, A., & Inoue, M. (1999) · PubMed · Cited by 509
Drug Resistance Driven by Cancer Stem Cells and Their Niche
Prieto‐Vila, M., Takahashi, R., Usuba, W., Kohama, I., & Ochiya, T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122574 · Cited by 526
Lendvay, T. S., Morris, D. K., Sah, J., Balasubramanian, B., & Lundblad, V. (1996) · Genetics · doi:10.1093/genetics/144.4.1399 · Cited by 503
Hallmarks of senescence in carcinogenesis and cancer therapy
Shay, J. W., & Roninson, I. B. (2004) · Oncogene · doi:10.1038/sj.onc.1207518 · Cited by 502
“Telomerase activity is present in almost all human tumors but not in adjacent normal cells (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundSelf-citationRegulation of telomere length and function by a Myb-domain protein in fission yeast
Cooper, J. P., Nimmo, E. R., Allshire, R. C., & Cech, T. R. (1997) · Nature · doi:10.1038/385744a0 · Cited by 503
Härle-Bachor, C., & Boukamp, P. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6476 · Cited by 492
Germline transmission of genetically modified primordial germ cells
van de Lavoir, M., Diamond, J. H., Leighton, P. A., Mather-Love, C., Heyer, B. S., Bradshaw, R., Kerchner, A., Hooi, L. T., Gessaro, T. M., Swanberg, S. E., et al. (2006) · Nature · doi:10.1038/nature04831 · Cited by 495
Kyo, S. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.3.669 · Cited by 499
Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors
Read, M., Harrison, R. J., Romagnoli, B., Tanious, F. A., Gowan, S. H., Reszka, A. P., Wilson, W. D., Kèlland, L. R., & Neidle, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081560598 · Cited by 504
Nanowire Sensors for Medicine and The Life Sciences
Patolsky, F., Zheng, G., & Lieber, C. M. (2006) · Nanomedicine · doi:10.2217/17435889.1.1.51 · Cited by 489
“Telomerase is inactive in most normal somatic cells but active in at least 80% of known human cancers [62], and thus is a detection of DNA and DNA reactions.”
BackgroundInteraction of Metal Complexes with G‐Quadruplex DNA
Georgiades, S. N., Karim, N. H. A., Suntharalingam, K., & Vilar, R. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.200906363 · Cited by 492
Telomere Position Effect in Human Cells
Baur, J. A., Zou, Y. S., Shay, J. W., & Wright, W. E. (2001) · Science · doi:10.1126/science.1062329 · Cited by 502
Self-citationDNA damage, cellular senescence and organismal ageing: causal or correlative?
Chen, J.-H., Hales, C. N., & Ozanne, S. E. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm681 · Cited by 507
“Most somatic cells have a finite number for population doubling and eventually become senescent because of telomere shortening due to the end replication problem (12,13).”
BackgroundTelomeres, stem cells, senescence, and cancer
Sharpless, N. E., & DePinho, R. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20761 · Cited by 488
Wright, W. E., Shay, J. W., & Piatyszek, M. A. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.18.3794 · Cited by 474
Self-citationLim, K. W., Amrane, S., Bouaziz, S., Xu, W., Mu, Y., Patel, D. J., Luu, K. N., & Phan, A. T. (2009) · Journal of the American Chemical Society · doi:10.1021/ja807503g · Cited by 480
Human telomeric DNA: G-quadruplex, i-motif and Watson-Crick double helix.
Phan, A., & Mergny, J. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf597 · Cited by 431
“In contrast to cancer cells, which often express high levels of telomerase ( 3 ), this activity is tightly regulated in normal human somatic cells (reviewed in 4). In a large number of organisms, telomeric DNA consists of highly repetitive short sequences.”
BackgroundHuman telomerase contains evolutionarily conserved catalytic and structural subunits
Harrington, L., Zhou, W., McPhail, T., Oulton, R., Yeung, D. S. K., Mar, V., Bass, M. B., & Robinson, M. O. (1997) · Genes & Development · doi:10.1101/gad.11.23.3109 · Cited by 465
“The lysates (5 µg of total protein) and immunoprecipitates (2 µl of protein G beads) were assayed by TRAP as described (Kim et al. 1994), and the remainder was subjected to SDS-PAGE and transferred to a PVDF membrane.”
BackgroundMethodInfluentialHPV‐mediated cervical carcinogenesis: concepts and clinical implications
Snijders, P. J. F., Steenbergen, R. D. M., Heideman, D. A. M., & Meijer, C. J. L. M. (2005) · The Journal of Pathology · doi:10.1002/path.1866 · Cited by 454
“Telomere erosion is considered to provide an intrinsic division count system that determines the lifespan of normal somatic cells [48].”
BackgroundArmanios, M., Chen, J.-L., Chang, Y.-P. C., Brodsky, R. A., Hawkins, A., Griffin, C. A., Eshleman, J. R., Cohen, A. R., Chakravarti, A., Hamosh, A., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508124102 · Cited by 452
The structure of telomeric DNA
Neidle, S., & Parkinson, G. N. (2003) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(03)00072-1 · Cited by 454
Takakura, M., Kyo, S., Kanaya, T., Hirano, H., Takeda, J., Yutsudo, M., & Inoue, M. (1999) · PubMed · Cited by 599
TERT promoter mutations in thyroid cancer
Liu, R., & Xing, M. (2016) · Endocrine Related Cancer · doi:10.1530/erc-15-0533 · Cited by 457
“0) Landa et al. (2013) 2/16 (12.”
BackgroundControl of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438
“using a telomere repeat amplification protocol (33) kit (Intergen Co.”
MethodThe telomerase reverse transcriptase: components and regulationPreprint
Nugent, C. I., & Lundblad, V. (1998) · Genes & Development · doi:10.1101/gad.12.8.1073 · Cited by 435
“Telomerase is not detectable in most human somatic cells and presumably as a consequence, telomere length recedes as cells replicate (Cooke and Smith 1986; Harley et al. 1990; Hastie et al. 1990; Kim et al. 1994).”
BackgroundTelomerase contributes to tumorigenesis by a telomere length-independent mechanism
Stewart, S. A., Hahn, W. C., O'Connor, B. F., Banner, E. N., Lundberg, A. S., Modha, P., Mizuno, H., Brooks, M. W., Fleming, M., Zimonjic, D. B., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182407599 · Cited by 431
Telomerase therapeutics for cancer: challenges and new directions
Shay, J. W., & Wright, W. E. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2081 · Cited by 442
Self-citationTelomerase activity in gastric cancer.
Hiyama, E., Yokoyama, T., Tatsumoto, N., Hiyama, K., Imamura, Y., Murakami, Y., Kodama, T., Piatyszek, M. A., Shay, J. W., & Matsuura, Y. (1995) · PubMed · Cited by 436
Self-citationBladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers
Lokeshwar, V. B., Habuchi, T., Grossman, H. B., Murphy, W. M., HAUTMANN, S. H., Hemstreet, G. P., Bono, A. V., Getzenberg, R. H., Goebell, P. J., Schmitz‐Dräger, B. J., et al. (2005) · Urology · doi:10.1016/j.urology.2005.08.064 · Cited by 430
Roberson, R. S., Kussick, S. J., Vallieres, E., Chen, S.-Y. J., & Wu, D. Y. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-1270 · Cited by 428
“Beyond M1, as cells further divide and telomeres shorten, a second restriction point (M2 or crisis) is encountered, at which time aberrant expression of telomerase or alternative telomeraseindependent mechanisms of telomere lengthening enables rare cells to traverse this restriction and become immortalized (12, 13).”
BackgroundA highly selective telomerase inhibitor limiting human cancer cell proliferation
Damm, K., Hemmann, U., Garin‐Chesa, P., Hauel, N., Kauffmann, I., Priepke, H., Niestroj, C., Daiber, C., Enenkel, B., Guilliard, B., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.6958 · Cited by 422
Ortiz-Montero, P., Londoño-Vallejo, A., & Vernot, J.-P. (2017) · Cell Communication and Signaling · doi:10.1186/s12964-017-0172-3 · Cited by 428
Multiple Tumor Suppressor Pathways Negatively Regulate Telomerase
Lin, S., & Elledge, S. J. (2003) · Cell · doi:10.1016/s0092-8674(03)00430-6 · Cited by 432
Senescence-associated inflammatory responses: aging and cancer perspectives
Lasry, A., & Ben-Neriah, Y. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.009 · Cited by 408
Telomerase Activity in Human Breast Tumors
Hiyama, E., Gollahon, L., Kataoka, T., Kuroi, K., Yokoyama, T., Gazdar, A. F., Hiyama, K., Piatyszek, M. A., & Shay, J. W. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.2.116 · Cited by 421
Self-citationPolymorphism of human telomeric quadruplex structures
Dai, J., Carver, M., & Yang, D. (2008) · Biochimie · doi:10.1016/j.biochi.2008.02.026 · Cited by 426
“Telomerase is activated in 80e85% of human cancer cells [21], and has been suggested to play a key role in maintaining the malignant phenotype by stabilizing telomere length and integrity [22].”
BackgroundHuman naive and memory T lymphocytes differ in telomeric length and replicative potential.
Weng, N., Levine, B. L., June, C. H., & Hodes, R. J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11091 · Cited by 418
Xu, C., Rosler, E. S., Jiang, J., LEBKOWSKI, J. S., Gold, J. D., O’Sullivan, C., Delavan‐Boorsma, K., Mok, M., Bronstein, A., & Carpenter, M. K. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0211 · Cited by 418
Telomere dysfunction and tumour suppression: the senescence connection
Deng, Y., Chan, S. S., & Chang, S. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2393 · Cited by 411
Greenberg, R. A., O’Hagan, R. C., Deng, H., Xiao, Q., Hann, S. R., Adams, R. R., Lichtsteiner, S., Chin, L., Morin, G. B., & DePinho, R. A. (1999) · Oncogene · doi:10.1038/sj.onc.1202669 · Cited by 411
“Moreover, in approximately 90% of all tumors, telomerase activity (Kim et al., 1994) as well as TERT expression (Nakamura et al., 1997; Meyerson et al., 1997; Harrington et al., 1997; Kilian et al., 1997; Nakayama et al., 1998) are detected.”
BackgroundMethodNucleic Acid-Based Methods for the Detection of Cancer
Sidransky, D. (1997) · Science · doi:10.1126/science.278.5340.1054 · Cited by 403
Regulated expression of telomerase activity in human T lymphocyte development and activation.
Weng, N., Levine, B. L., June, C. H., & Hodes, R. J. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2471 · Cited by 401
Human telomerase RNA and telomerase activity in immortal cell lines and tumor tissues.
Avilion, A. A., Piatyszek, M. A., Gupta, J., Shay, J. W., Bacchetti, S., & Greider, C. W. (1996) · PubMed · Cited by 399
Self-citationTelomerase activity, cell proliferation, and cancer
Greider, C. W. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.90 · Cited by 408
Cellular senescence, cancer and aging: the telomere connection
Campisi, J., Kim, S.-H., Lim, C.-S., & Rubio, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00160-7 · Cited by 400
Transformation of primary human endothelial cells by Kaposi's sarcoma-associated herpesvirus
Flore, O., Rafii, S., Ely, S. A., O’Leary, J. J., Hyjek, E. M., & Cesarman, E. (1998) · Nature · doi:10.1038/29093 · Cited by 399
“The enzyme telomerase is essential to maintain the telomere length of chromosomes and to enable cells to proliferate indefinitel”
BackgroundCritical pathways in cellular senescence and immortalization revealed by gene expression profiling
Fridman, A. L., & Tainsky, M. A. (2008) · Oncogene · doi:10.1038/onc.2008.213 · Cited by 385
“This rare cell escapes crisis and becomes immortalized through telomere stabilization either by telomerase activation or alternate lengthening of telomeres (Bischoff et al., 1990; Kim et al., 1994; Bodnar et al., 1998; Gollahon et al., 1998; Cong et al., 2002).”
BackgroundYudoh, K., van Trieu, N., Nakamura, H., Masuko, K., Kato, T., & Nishioka, K. (2005) · Arthritis Research & Therapy · doi:10.1186/ar1499 · Cited by 397
“Telomere length was determined using terminal restriction fragment Southern blot analysis, as described previously [35,36].”
MethodDai, J., Punchihewa, C., Ambrus, A., Ding, C., Jones, R. A., & Yang, D. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm009 · Cited by 403
“002 RMSD of dihedral angle violation (8) 1.”
BackgroundChiu, C., Dragowska, W., Kim, N. W., Vaziri, H., Yui, J., Thomas, T. E., Harley, C. B., & Lansdorp, P. M. (1996) · STEM CELLS · doi:10.1002/stem.140239 · Cited by 388
Self-citationTelomere lengthening early in development
Liu, L., Bailey, S. M., Okuka, M., Muñoz, P., Li, C., Zhou, L., Wu, C., Czerwiec, E., Sandler, L., Seyfang, A., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1664 · Cited by 405
“dtd" [ ]> Stem cells and cancer cells maintain telomere length mostly through telomeras”
Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene.
Horikawa, I., Cable, P. L., Afshari, C. A., & Barrett, J. C. (1999) · PubMed · Cited by 393
Telomerase Activity in Hematopoietic Cells Is Associated with Self-Renewal Potential
Morrison, S. J., Prowse, K. R., Ho, P., & Weissman, I. L. (1996) · Immunity · doi:10.1016/s1074-7613(00)80316-7 · Cited by 394
Self-citationCell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands
Riou, J., Guittat, L., Mailliet, P., Laoui, A., Renou, E., Petitgenet, O., Mégnin-Chanet, F., Hélène, C., & Mergny, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052698099 · Cited by 411
Guðjónsson, Þ., Villadsen, R., Nielsen, H. L., Rønnov‐Jessen, L., Bissell, M. J., & PETERSEN, O. W. (2002) · Genes & Development · doi:10.1101/gad.952602 · Cited by 390
“Third, studies of other organs, including liver, pancreas, skin, testes, and prostate have revealed that the stem cell compartment expresses keratin K19 (Stosiek et al. 1990; Fridmacher et al. 1995; Michel et al. 1996; Bouwens 1998; Hudson et al. 2001).”
BackgroundVaziri, H., West, M. D., Allsopp, R., Davison, T. S., Wu, Y., Arrowsmith, C. H., Poirier, G. G., & Benchimol, S. (1997) · The EMBO Journal · doi:10.1093/emboj/16.19.6018 · Cited by 384
“…of p53 protein increases with cell age in ase in immortal cells provides one mechanism for thethe absence of any marked increase in the level of p53 prevention of telomere shortening (Morin, 1989; Counterprotein, and that p21WAF1 promoter activity in senescent et al., 1992; Kim et al., 1994).”
BackgroundSelf-citationThe non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase
Redon, S., Reichenbach, P., & Lingner, J. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq296 · Cited by 385
“Since direct telomerase assays do not involve PCR amplification as done in the TRAP assay (22), information on telomerase processivity can be obtained (see below).”
BackgroundAn RNA-dependent RNA polymerase formed by TERT and the RMRP RNA
Maida, Y., Yasukawa, M., Furuuchi, M., Lassmann, T., Possemato, R., Okamoto, N., Kasim, V., Hayashizaki, Y., Hahn, W. C., & Masutomi, K. (2009) · Nature · doi:10.1038/nature08283 · Cited by 384
Telomere Dysfunction Increases Mutation Rate and Genomic Instability
Hackett, J. A., Feldser, D. M., & Greider, C. W. (2001) · Cell · doi:10.1016/s0092-8674(01)00457-3 · Cited by 386
Piatyszek, M. A., Kim, N. W., Weinrich, S. L., Hiyama, K., Hiyama, E., Wright, W. E., & Shay, J. W. (1995) · Methods in Cell Science · doi:10.1007/bf00981880 · Cited by 383
Self-citationAxis of ageing: telomeres, p53 and mitochondria
Sahin, E., & DePinho, R. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3352 · Cited by 345
Expression of TERT in early premalignant lesions and a subset of cells in normal tissues
Kolquist, K. A., Ellisen, L. W., Counter, C. M., Meyerson, M. M., Tan, L. K., Weinberg, R. A., Haber, D. A., & Gerald, W. L. (1998) · Nature Genetics · doi:10.1038/554 · Cited by 382
“This progression is accompanied by the accumulation of genetic alteration”
BackgroundPhysical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Werner, C., Fürster, T., Widmann, T., Pöss, J., Roggia, C., Hanhoun, M., Scharhag, J., Büchner, N., Meyer, T., Kindermann, W., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.861005 · Cited by 380
Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening
Zhu, J., Wang, H., Bishop, J. M., & Blackburn, E. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3723 · Cited by 382
Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations
Diaz de Leon, A., Cronkhite, J. T., Katzenstein, A.-L. A., Godwin, J. D., Raghu, G., Glazer, C. S., Rosenblatt, R. L., Girod, C. E., Garrity, E. R., Xing, C., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010680 · Cited by 377
“hTERT is highly expressed in germ cells, cells with proliferative potential and immortalized cancer cells[3,4,5].”
BackgroundShi, S., Gronthos, S., Chen, S., Reddi, A. H., Counter, C. M., Robey, P. G., & Wang, C.-Y. (2002) · Nature Biotechnology · doi:10.1038/nbt0602-587 · Cited by 379
Catalytic Beacons for the Detection of DNA and Telomerase Activity
Xiao, Y., Pavlov, V. V., Niazov, T., Dishon, A., Kotler, M., & Willner, I. (2006) · Springer eBooks · doi:10.1007/1-4020-3384-2_15 · Cited by 376
Nakayama, J., Saito, M., Nakamura, H., Matsuura, A., & Ishikawa, F. (1997) · Cell · doi:10.1016/s0092-8674(00)81933-9 · Cited by 376
Ex vivo enrichment of mesenchymal cell progenitors by fibroblast growth factor 2
Bianchi, G., Banfi, A., Mastrogiacomo, M., Notaro, R., Luzzatto, L., Cancedda, R., & Quarto, R. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00138-1 · Cited by 374
Morrow, D. M., Tagle, D. A., Shiloh, Y., Collins, F. S., & Hieter, P. (1995) · Cell · doi:10.1016/0092-8674(95)90480-8 · Cited by 370
Short Dysfunctional Telomeres Impair Tumorigenesis in the INK4aΔ2/3 Cancer-Prone Mouse
Greenberg, R. A., Chin, L., Femino, A., Lee, K.-H., Gottlieb, G. J., Singer, R. H., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80761-8 · Cited by 367
Structure of Human Telomeric DNA in Crowded Solution
Heddi, B., & Phan, A. T. (2011) · Journal of the American Chemical Society · doi:10.1021/ja200786q · Cited by 379
The terminal DNA structure of mammalian chromosomes
McElligott, R., & Wellinger, R. J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3705 · Cited by 379
Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.
Izbicka, E., Wheelhouse, R. T., Raymond, É., Davidson, K. K., Lawrence, R. A., Sun, D., Windle, B. E., Hurley, L. H., & Hoff, D. D. V. (1999) · PubMed · Cited by 358
Calado, R. T., Yewdell, W. T., Wilkerson, K. L., Regal, J. A., Kajigaya, S., Stratakis, C. A., & Young, N. S. (2009) · Blood · doi:10.1182/blood-2008-09-178871 · Cited by 373
The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells.
Dimri, G. P., Martínez‐Guitarte, J., Jacobs, J. J. L., Keblusek, P., Itahana, K., van Lohuizen, M., Campisi, J., Wazer, D. E., & Band, V. (2002) · PubMed · Cited by 357
Metadata
- Authors
- Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W.
- Affiliations
- Geron (United States) (US)
- The University of Texas Southwestern Medical Center (US)
- Geron Corporation, Menlo Park, CA 94025.
- Venue
- Science
- Published
- 1994-12-23
- Volume
- 266
- Issue
- 5193
- Pages
- 2011-2015
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2000971601
- Cited by
- 7,091
- References
- 32
- Citations by year
- 2026: 51 · 2025: 104 · 2024: 109 · 2023: 175 · 2022: 140 · 2021: 209 · 2020: 182 · 2019: 181 · 2018: 208 · 2017: 209 · 2016: 235 · 2015: 232 · 2014: 228 · 2013: 222 · 2012: 235
- FWCI
- 85.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r43ca065178-01, 5r01ca050195-05)
- National Institute on Aging (AG07992, R01AG007992)
- National Cancer Institute (CA 50195, CA65178)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- telomerase, telomerase activity assay, cellular immortality, cancer, tumor growth, telomere synthesis, benign tumors, cell proliferation
- MeSH terms
- Base Sequence, Cell Division, Cell Line, Cell Line, Transformed, DNA Nucleotidylexotransferase, Enzyme Activation, Enzyme Repression, Female, Humans, Male, Molecular Sequence Data, Neoplasms, Ovary, Testis, Tumor Cells, Cultured, Polymerase Chain Reaction
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