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).
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Items 901–1,000 of 1,043
Altmeyer, A., Maki, R. G., Feldweg, A. M., Heike, M., Protopopov, V., Masur, S. K., & Srivastava, P. K. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960822)69:4 · Cited by 174
Phthalocyanines: a new class of G-quadruplex-ligands with many potential applications
Yaku, H., Fujimoto, T., Murashima, T., Miyoshi, D., & Sugimoto, N. (2012) · Chemical Communications · doi:10.1039/c2cc31037f · Cited by 119
Large-scale parent–child comparison confirms a strong paternal influence on telomere length
Nordfjäll, K., Svenson, U., Norrback, K., Adolfsson, R., & Roos, G. (2009) · European Journal of Human Genetics · doi:10.1038/ejhg.2009.178 · Cited by 110
Hänsel, R., Foldynová-Trantírková, S., Löhr, F., Buck, J., Bongartz, E.-V., Bamberg, E., Schwalbe, H., Dötsch, V., & Trantı́rek, L. (2009) · Journal of the American Chemical Society · doi:10.1021/ja9052027 · Cited by 118
Genome-Wide Association Study of Relative Telomere Length
Prescott, J., Kraft, P. L., Chasman, D. I., Savage, S. A., Mirabello, L. J., Berndt, S. I., Weissfeld, J. L., Han, J., Hayes, R. B., Chanock, S. J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019635 · Cited by 112
“In germ cells, strong telomerase expression maintains long telomere lengths [10].”
BackgroundKyte, J. A., Gaudernack, G., Dueland, S., Trachsel, S., Julsrud, L., & Aamdal, S. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0184 · Cited by 111
Walton, N. M., Sutter, B. M., Chen, H., Chang, L., Roper, S. N., Scheffler, B., & Steindler, D. A. (2006) · Development · doi:10.1242/dev.02541 · Cited by 113
“However, telomerase has been detected in germ cells (Kim et al., 1994) and hematopoietic cells in vivo (Broccoli et al., 1995; Counter et al., 1995; Hiyama et al., 1995), and can be attenuated by physiological alterations in endometrial cells (Kyo et al., 1997), suggesting it may possible to induce…”
BackgroundWanted DEAD/H or Alive: Helicases Winding Up in Cancers
Cai, W., Chen, Z. X., Rane, G., Singh, S. S., Choo, Z., Wang, C., Yuan, Y., Tan, T. Z., Arfuso, F., Yap, C. T., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw278 · Cited by 116
Telomere Length Dynamics and DNA Damage Responses Associated with Long-Duration Spaceflight
Luxton, J. J., McKenna, M. J., Lewis, A. M., Taylor, L. E., George, K. A., Dixit, S. M., Moniz, M., Benegas, W., MacKay, M. J., Mozsary, C., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108457 · Cited by 114
Santillano, D. R., Kumar, L. S., Prock, T. L., Camarillo, C., Tingling, J. D., & Miranda, R. C. (2005) · BMC Neuroscience · doi:10.1186/1471-2202-6-59 · Cited by 113
“Telomerase is active in all germline tissues, transformed cells and most human cancers [38,39], but is particularly robust during neurogenesis where it has been shown to function as an anti-apoptotic factor in developing neurons [40,41].”
BackgroundMethodWang, Z., Kyo, S., Takakura, M., Tanaka, M., Yatabe, N., Maida, Y., Fujiwara, M., Hayakawa, J., Ohmichi, M., Koike, K., et al. (2000) · PubMed · Cited by 116
Majumdar, A. S., Hughes, D. E., Lichtsteiner, S., Wang, Z., LEBKOWSKI, J. S., & Vasserot, A. P. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301421 · Cited by 113
Nuclear PARPs and genome integrityPreprint
Azarm, K., & Smith, S. H. (2020) · Genes & Development · doi:10.1101/gad.334730.119 · Cited by 116
“1996), but is up-regulated in most human cancers (Kim et al. 1994) and is required for tumor cell growth (Hahn et al.”
BackgroundTelomere and adaptive immunity
Weng, N.-P. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.11.005 · Cited by 99
Ou, T., Lin, J., Lu, Y., Hou, J., Tan, J., Chen, S., Li, Z., Li, Y., Li, D., Gu, L., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200062u · Cited by 112
Regulation of the Telomerase Reverse Transcriptase Subunit through Epigenetic Mechanisms
Lewis, K. A., & Tollefsbol, T. O. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00083 · Cited by 112
“Approximately 90% of all human cancers contain an increased level of telomerase (Figure 1), and understanding the epigenetic regulation of the gene that encodes for the TERT subunit provides a mechanism for controlling its expression (Kim et al., 1994).”
BackgroundEnzyme Inhibitors and Activators
Şentürk, M. (2017) · InTech eBooks · doi:10.5772/63325 · Cited by 113
Extensive Proliferation of Human Cancer Cells with Ever-Shorter Telomeres
Dagg, R. A., Pickett, H. A., Neumann, A. A., Napier, C. E., Henson, J. D., Teber, E., Arthur, J. W., Reynolds, C. P., Murray, J. E., Haber, M., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.05.087 · Cited by 110
In vitro assays and techniques utilized in anticancer drug discovery
Ediriweera, M. K., Tennekoon, K. H., & Samarakoon, S. R. (2018) · Journal of Applied Toxicology · doi:10.1002/jat.3658 · Cited by 116
“In the extension step, addition of telomere repeats to telomere substrate by the enzyme telomerase occurs and in the amplification step, telomere products are amplified by the PCR using specific primers (Kim et al., 1994;Mender & Shay, 2015).”
MethodInfluentialTheories of Aging: An Ever-Evolving Field
Владимирович, С. П., Dontsova, O. А., & Berezkin, G. V. (2015) · Acta Naturae · doi:10.32607/20758251-2015-7-1-9-18 · Cited by 116
Relevance of Urine Telomerase in the Diagnosis of Bladder Cancer
Sanchini, M. A. (2005) · JAMA · doi:10.1001/jama.294.16.2052 · Cited by 112
Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo
Shammas, M. A., Koley, H., Bertheau, R. C., Neri, P., Fulciniti, M., Tassone, P., Blotta, S., Protopopov, A. I., Mitsiades, C. S., Batchu, R. B., et al. (2008) · Leukemia · doi:10.1038/leu.2008.81 · Cited by 112
Warner, J. K., Wang, J. C. Y., Takenaka, K., Doulatov, S. R., McKenzie, J. L., Harrington, L. A., & Dick, J. E. (2005) · Leukemia · doi:10.1038/sj.leu.2403917 · Cited by 118
Replication of Wild-Type and Mutant Human Cytomegalovirus in Life-Extended Human Diploid Fibroblasts
Bresnahan, W. A., Hultman, G. E., & Shenk, T. E. (2000) · Journal of Virology · doi:10.1128/jvi.74.22.10816-10818.2000 · Cited by 112
“As a negative control, equivalent cell lysates from all samples were incubated at 85°C for 10 min to inactivate telomerase activity (2, 7).”
MethodTelomeres and Human Somatic Fitness
Aviv, A. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.8.871 · Cited by 112
“It may not be a coincidence that most cancers demonstrate robust activity of telomerase (36) or have resorted to the alternate (ALT) pathway (37), which employs mechanisms other than telomerase to dodge the telomeric barrier.”
BackgroundTranscriptional Targeting in Cancer Gene Therapy
Robson, T., & Hirst, D. G. (2003) · BioMed Research International · doi:10.1155/s1110724303209074 · Cited by 115
“Approximately 90% of human cancers possess active telomerase, whereas normal somatic tissues have either much lower or undetectable activity [79, 80, 81].”
BackgroundTRF1, a mammalian telomeric protein
Smith, S. H., & de Lange, T. (1997) · Trends in Genetics · doi:10.1016/s0168-9525(96)10052-4 · Cited by 113
Zheng, G., Daniel, W. L., & Mirkin, C. A. (2008) · Journal of the American Chemical Society · doi:10.1021/ja803035p · Cited by 112
A three-state model for the regulation of telomerase by TERRA and hnRNPA1
Redon, S., Zemp, I., & Lingner, J. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt695 · Cited by 111
“The TS-primer has been extensively used in TRAP-telomerase assays (29).”
MethodEvolution of telomere maintenance and tumour suppressor mechanisms across mammals
Tian, X., Doerig, K. R., Park, R., Qin, A. C. R., Hwang, C., Neary, A., Gilbert, M. B., Seluanov, A., & Gorbunova, V. A. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0443 · Cited by 109
“Telomerase activity measured by the TRAP assay [4] across seven organs showed a very strong negative correlation with species body mass, but not with MLS [5] (figure 2).”
BackgroundMethodTelomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 120
Mitochondria, Telomeres and Telomerase Subunits
Zheng, Q., Huang, J., & Wang, G. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00274 · Cited by 118
TERT Promoter Alterations in Glioblastoma: A Systematic Review
Olympios, N., Gilard, V., Marguet, F., Clatot, F., Fiore, F. D., & Fontanilles, M. (2021) · Cancers · doi:10.3390/cancers13051147 · Cited by 125
“Telomeres shorten at every cell cycle, eventually leading to cell death or senescence [11].”
BackgroundTelomerase activity in the subventricular zone of adult mice
Caporaso, G. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00103-9 · Cited by 113
Parkhurst, M. R., Riley, J. P., Igarashi, T., Li, Y., Robbins, P. F., & Rosenberg, S. A. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0325 · Cited by 111
Telomere dysfunction alters the chemotherapeutic profile of transformed cells
Lee, K.-H., Rudolph, K. L., Ju, Y.-J., Greenberg, R. A., Cannizzaro, L. A., Chin, L., Weiler, S. R., & DePinho, R. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051629198 · Cited by 111
Aging and cancer: are telomeres and telomerase the connection?
Shay, J. W. (1995) · Molecular Medicine Today · doi:10.1016/s1357-4310(95)93872-9 · Cited by 109
Self-citationSexton, A. N., Regalado, S. G., Lai, C. S., Cost, G. J., O’Neil, C. M., Urnov, F. D., Gregory, P. D., Jaenisch, R., Collins, K., & Hockemeyer, D. F. (2014) · Genes & Development · doi:10.1101/gad.246819.114 · Cited by 112
“…residual wild-type protein but also tumor-specific alterations in chromosome number and the aberrant process of telomerase activation in tumor cells (Kim et al. 1994; Bryan et al. 1998; Nakashima et al. 2013), which could change the physiological requirements for telomerase access to telomeres.”
BackgroundMethodKirwan, M., Vulliamy, T., Marrone, A., Walne, A. J., Beswick, R., Hillmen, P., Kelly, R., Stewart, A., Bowen, D., Schonland, S. O., et al. (2009) · Human Mutation · doi:10.1002/humu.21115 · Cited by 109
“Telomerase activity of 3,000 cells was measured by the telomeric repeat amplification protocol (TRAP) [Kim et al., 1994] using the TRAPeze RT Telomerase Detection Kit (Millipore, Bedford, MA/ Chemicon, Temecula, CA) according to manufacturer’s instructions.”
MethodThe role of telomeres in the ageing of human skin: Telomeres and skin ageing
Buckingham, E. M., & Klingelhutz, A. J. (2011) · Experimental Dermatology · doi:10.1111/j.1600-0625.2010.01242.x · Cited by 109
Zhang, M., Wang, Z., Obazee, O. M., Jia, J., Childs, E. J., Hoskins, J. W., Figlioli, G., Mocci, E., Collins, I. J., Chung, C. C., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11041 · Cited by 110
“The TERT gene encodes the catalytic subunit of telomerase, known for its critical role in maintaining telomere ends and the increased telomerase activity frequently seen in human cancers [63-65].”
BackgroundLiu, W., Zhong, Y.-F., Liu, L., Shen, C.-T., Zeng, W., Wang, F., Yang, D., & Mao, Z. (2018) · Nature Communications · doi:10.1038/s41467-018-05810-4 · Cited by 110
Telomere Maintenance Mechanisms Define Clinical Outcome in High-Risk Neuroblastoma
Koneru, B., López, G., Farooqi, A. S., Conkrite, K. L., Nguyen, T. H., Macha, S. J., Modi, A., Rokita, J. L., Urias, E., Hindle, A., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3068 · Cited by 112
“Unlimited proliferation of cancer cells requires that they maintain telomeres (1), which are typically maintained by activating telomerase (2).”
BackgroundMethodHampel, S. M., Sidibe, A., Gunaratnam, M., Riou, J., & Neidle, S. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.09.066 · Cited by 110
Wu, H. L., Hsu, C. Y., Liu, W. H., & Yung, B. Y. (1999) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19990611)81:6 · Cited by 110
Telomeres: Prognostic markers for solid tumors
Bisoffi, M., Heaphy, C. M., & Griffith, J. K. (2006) · International Journal of Cancer · doi:10.1002/ijc.22120 · Cited by 110
Trujillo, K. A., Heaphy, C. M., Mai, M., Vargas, K. M., Jones, A. C., Vo, P., Butler, K. S., Joste, N. E., Bisoffi, M., & Griffith, J. K. (2010) · International Journal of Cancer · doi:10.1002/ijc.25788 · Cited by 110
Use of exogenous hTERT to immortalize primary human cells
Lee, K. M., Choi, K. H., & Ouellette, M. M. (2004) · Cytotechnology · doi:10.1007/10.1007/s10616-004-5123-3 · Cited by 121
“In most primary human cells, hTERT and telomerase activity are either absent or present at levels that are insufficient for telomere maintenance (Kim et al. 1994; Shay and Bacchetti 1997; Masutomi et al. 2003).”
BackgroundRole of Telomerase in Cell Senescence and Oncogenesis
Urquidi, V., Tarin, D., & Goodison, S. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.65 · Cited by 110
Alternative Lengthening of Telomeres in Human Cells
Reddel, R. R., Bryan, T. M., Colgin, L. M., Perrem, K., & Yeager, T. R. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0194:alotih]2.0.co;2 · Cited by 109
Lin, T.-Y., Huang, X., Gu, J. H., Zhang, L., Roth, J. A., Xiong, M., Curley, S. A., Yu, Y., Hunt, K. K., & Fang, B. (2002) · Oncogene · doi:10.1038/sj.onc.1205926 · Cited by 110
“…we also demonstrated that the human telomerase reverse transcriptase (hTERT) promoter, whose gene is active in more than 85% of human cancers but quiescent in most somatic cells (Kim et al., 1994; Shay and Bacchetti, 1997), could be used to target proapoptotic genes to cancers (Gu et al., 2000).”
BackgroundKohn, K. W., Zeeberg, B. M., Reinhold, W. C., & Pommier, Y. G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099269 · Cited by 109
“GRHL2 also stimulates the expression of PCNA and is generally expressed in carcinomas, but not in normal tissues [53,54].”
BackgroundXiao, Y., Dane, K. Y., Uzawa, T., Csordas, A. T., Qian, J., Soh, H. T., Daugherty, P. S., Lagally, E. T., Heeger, A. J., & Plaxco, K. W. (2010) · Journal of the American Chemical Society · doi:10.1021/ja106513f · Cited by 109
Telomere and Telomerase Therapeutics in Cancer
Xu, Y., & Goldkorn, A. (2016) · Genes · doi:10.3390/genes7060022 · Cited by 113
“This assay consists of two steps, an extension reaction in which a “telomerase substrate” (TS) oligonucleotide mimicking a 3’ telomere end is combined with cell lysate containing telomerase, and an amplification reaction in which any TS oligo extended by telomerase in the lysate is PCR amplified for detection [71].”
MethodBODIPY based metal-organic macrocycles and frameworks: Recent therapeutic developments
Gupta, G., Sun, Y., Das, A. K., Stang, P. J., & Lee, C. Y. (2021) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2021.214308 · Cited by 111
Marek’s disease virus: lytic replication, oncogenesis and control
Jarosinski, K. W., Tischer, B. K., Trapp, S., & Osterrieder, N. (2006) · Expert Review of Vaccines · doi:10.1586/14760584.5.6.761 · Cited by 116
Total Syntheses of the Telomerase Inhibitors Dictyodendrin B, C, and E
Fürstner, A., Domostoj, M. M., & Scheiper, B. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0617800 · Cited by 109
Kim, E., Kim, J.-H., Shin, H. Y., Lee, H., Yang, J. M., Kim, J., Sohn, J., Kim, H., & Yun, C. (2003) · Human Gene Therapy · doi:10.1089/104303403769211637 · Cited by 109
Venetsanakos, E., Mirza, A. M., Fanton, C. P., Romanov, S. R., Tlsty, T. D., & McMahon, M. (2002) · Experimental Cell Research · doi:10.1006/excr.2001.5424 · Cited by 109
“[14] and as outlined in the Boehringer TRAP assay kit (Boehringer”
MethodTelomere Length in Fibroblasts and Blood Cells from Healthy Centenarians
Mondello, C., Petropoulou, C., Monti, D., GONOS, E., Franceschi, C., & Nuzzo, F. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4398 · Cited by 109
Garcia‐Aranda, C., de Juan, C., Diaz‐Lopez, A., Sanchez‐Pernaute, A., Torres, A., Diaz‐Rubio, E., Balibrea, J., Benito, M., & Iniesta, P. (2006) · Cancer · doi:10.1002/cncr.21625 · Cited by 105
“the activity of telomerase by serial dilutions of each extract, as described previously.(13)”
MethodJagadeesh, S., Kyo, S., & Banerjee, P. P. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2494 · Cited by 107
“This enzyme is present in germ line cells, cancer-derived cell lines, and spontaneously immortalized cells in culture and is activated in 85% to 90% malignant tumors but usually absent in normal somatic cells, which results in the progressive loss of telomeres with each cell division (3).”
BackgroundEom, G., Kim, H., Hwang, A., Son, H. Y., Choi, Y., Moon, J., Kim, D., Lee, M., Lim, E., Jeong, J., et al. (2017) · Advanced Functional Materials · doi:10.1002/adfm.201701832 · Cited by 108
Origin, Diversity, and Evolution of Telomere Sequences in Plants
Peška, V., & Garcia, S. (2020) · Frontiers in Plant Science · doi:10.3389/fpls.2020.00117 · Cited by 109
Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids
Perrem, K., Bryan, T. M., Englezou, A., Hackl, T., Moy, E. L., & Reddel, R. R. (1999) · Oncogene · doi:10.1038/sj.onc.1202752 · Cited by 116
“Telomere repeat ampli®cation protocol (TRAP) assay The PCR based TRAP assay for telomerase activity was used as described (Kim et al., 1994).”
BackgroundMethodLansdorp, P. M. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.172 · Cited by 109
Total Synthesis of Dictyodendrin B
Fürstner, A., Domostoj, M. M., & Scheiper, B. (2005) · Journal of the American Chemical Society · doi:10.1021/ja0541175 · Cited by 108
Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma
Ridley, L., Rahman, R., Bründler, M., Ellison, D. W., Lowe, J. S., Robson, K., Prebble, E., Luckett, I., Gilbertson, R. J., Parkes, S. E., et al. (2008) · Neuro-Oncology · doi:10.1215/15228517-2008-036 · Cited by 108
Chiang, Y. J., Hemann, M. T., Hathcock, K. S., Tessarollo, L., Feigenbaum, L., Hahn, W. C., & Hodes, R. J. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7024-7031.2004 · Cited by 107
“Knockout mice that are completely deficient in mTERT also lack telomerase activity (19, 27), and telomere shortening has been reported to occur over successive generations of these mTERT-deficient mice (35; unpublished data).”
BackgroundBolonaki, I., Kotsakis, A. P., Papadimitraki, E., Aggouraki, D., Konsolakis, G., Vagia, A., Christophyllakis, C., Nikoloudi, I., Magganas, E., Galanis, A., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.3465 · Cited by 108
“The telomerase reverse transcriptase (TERT) subunit is a promising target for cancer immunotherapy as it is overexpressed in many human tumors and, therefore, is considered a universal tumor antigen, whereas most normal human tissues do not express TERT.(12-14) TERT is overexpressed in more than 85% of NSCLC and is as…”
BackgroundTelomerase Expression Predicts Unfavorable Outcome in Osteosarcoma
Sanders, R. P., Drissi, R., Billups, C. A., Daw, N. C., Valentine, M. B., & Dome, J. S. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.03.043 · Cited by 108
An in vitro assay for saccharomyces telomerase requires EST1
Lin, J., & Zakian, V. A. (1995) · Cell · doi:10.1016/s0092-8674(05)80017-0 · Cited by 108
Igarashi, H., & Sakaguchi, N. (1997) · Blood · doi:10.1182/blood.v89.4.1299 · Cited by 108
Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells
Nagpal, N., Wang, J., Zeng, J., Lo, E., Moon, D. H., Luk, K., Braun, R. O., Burroughs, L. M., Keel, S. B., Reilly, C., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.03.016 · Cited by 105
“When primary fibroblasts were transduced with a retrovirus encoding TERT, both BCH001-treated and untreated cells were immortalized, but only cells treated with BCH001 showed telomere lengthening (Figure 4H).”
BackgroundInfluentialTakakura, M., Kyo, S., Inoue, M., Wright, W. E., & Shay, J. W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.18.8037-8043.2005 · Cited by 107
“Detectable telomerase activity is observed only in some highly regenerative tissues such as hematopoietic progenitor, intestinal crypt, skin basal layer, cervical keratinocyte, endometrium, and germ line cells; however, 75 to 85% of cancer cells show telomerase activity (9, 13, 16, 21 , 23, 25, 37, 43).”
BackgroundSelf-citationCaveolin-1, cellular senescence and age-related diseases
Zou, H., Stoppani, E., Volonte, D., & Galbiati, F. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.11.001 · Cited by 112
“Cellular senescence and aging Most cells cannot divide indefinitely due to a process termed cellular senescence (Black et al., 2000; Dimri et al., 1995; Kim et al., 1994; Lee et al., 1998; Lundberg et al., 2000; Sherr and DePinho, 2000; Wynford-Thomas, 1999).”
BackgroundA balance between elongation and trimming regulates telomere stability in stem cells
Rivera, T., Haggblom, C., Cosconati, S., & Karlseder, J. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3335 · Cited by 108
Hybrid-type and two-tetrad antiparallel telomere DNA G-quadruplex structures in living human cells
Bao, H., Liu, H.-S., & Xu, Y. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz276 · Cited by 107
“The enzyme telomerase is activated in 80% of human cancer cells (6,7).”
BackgroundRagupathi, A., Singh, M., Perez, A. M., & Zhang, D. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1133472 · Cited by 120
“85–90% of cancers manifest robust telomerase activity (TEL+) (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundTerahertz Photons Inhibit Cancer Cells Long Term by Suppressing Nano Telomerase Activity
Yin, J., Wu, K., Yu, Y., Zhong, Y., Song, Z., Chang, C., & Liu, G. (2024) · ACS Nano · doi:10.1021/acsnano.3c09216 · Cited by 108
Buschini, A., Pinelli, S., Pellacani, C., Giordani, F., Ferrari, M. B., Bisceglie, F., Giannetto, M., Pelosi, G., & Tarasconi, P. (2009) · Journal of Inorganic Biochemistry · doi:10.1016/j.jinorgbio.2008.12.016 · Cited by 107
Telomere length mediates the effects of telomerase on the cellular response to genotoxic stress
Rubio, M. Á., Davalos, A. R., & Campisi, J. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.004 · Cited by 105
Tissue-specific promoters for cancer gene therapy
Saukkonen, K., & Hemminki, A. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.5.683 · Cited by 108
“Telomerase activity is high in almost all human tumours and, therefore, the hTERT promoter could be useful for restricting CRAD replication to cancer cells, irrespective of their tissue of origin [80,81].”
BackgroundTelomerase activity and the expression of telomerase components in acute myelogenous leukaemia
Xu, D., Gruber, A., Peterson, C. O., & Pisa, P. (1998) · British Journal of Haematology · doi:10.1046/j.1365-2141.1998.00969.x · Cited by 107
“A commercial telomerase PCR ELISA kit (Boehringer Mannheim, Mannheim, Germany), based on TRAP introduced by Kim et al (1994), was used to determine telomerase activity in all specimens.”
BackgroundMethodTelomerase Activity Does Not Always Imply Telomere Maintenance
Ouellette, M. M., Aisner, D. L., Savre‐Train, I., Wright, W. E., & Shay, J. W. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.0114 · Cited by 106
Self-citationDome, J. S., CHUNG, S. S., Bergemann, T. L., Umbricht, C. B., Saji, M., Carey, L., Grundy, P. E., Perlman, E. J., Breslow, N. E., & Sukumar, S. V. (1999) · PubMed · Cited by 107
Narala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-09-0965 · Cited by 106
“Consistent with this model telomerase is reactivated in immortal human cells (Counter et al., 1992; Kim et al., 1994).”
BackgroundDorsey, J. F., Kao, G. D., MacArthur, K. M., Ju, M., Steinmetz, D., Wileyto, E. P., Simone, C. B., & Hahn, S. M. (2014) · Cancer · doi:10.1002/cncr.28975 · Cited by 106
“1).(21,32,33) It is noteworthy that an early effort also detected telomerase activity in the epithelial cell fraction harvested from the Figure 4.”
BackgroundTelomeres in aging and disease: lessons from zebrafish
Carneiro, M. C., de Castro, I. P., & Ferreira, M. G. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.025130 · Cited by 109
“In contrast, the majority of differentiated somatic cells have no detectable levels of telomerase (Kim et al., 1994).”
InfluentialSalloum, R., Hummel, T. R., Kumar, S. S., Dorris, K. M. O., Li, S., Lin, T., Daryani, V. M., Stewart, C. F., Miles, L., Poussaint, T. Y., et al. (2016) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2189-7 · Cited by 106
“While telomerase activity is undetectable in most normal tissues, it is increased in about 90 % of cancers [2, 3].”
BackgroundXiong, C., Liang, W., Zheng, Y., Zhuo, Y., Chai, Y., & Yuan, R. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b00259 · Cited by 106
Eisenberg, D. T. A., & Kuzawa, C. W. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0442 · Cited by 108
Molecular mechanisms of telomere biology disorders
Grill, S., & Nandakumar, J. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.014017 · Cited by 114
“Indeed, telomerase is upregulated in over 90% of all cancers (6).”
BackgroundAntisense therapeutics: from theory to clinical practice
Pirollo, K. F., Rait, A. S., Sleer, L. S., & Chang, E. H. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(03)00053-6 · Cited by 107
“Telomerase activity is evident in most malignant tumors, but is not detectable in normal somatic tissues, with the exception of embryonic cells, adult male germline cells, and proliferative cells of normal tissues (Kim et al., 1994; Shay, 1995; Shay & Gazdar, 1997).”
BackgroundFusenig, N. E., & Boukamp, P. (1998) · Molecular Carcinogenesis · doi:10.1002/(sici)1098-2744(199811)23:3 · Cited by 287
Guyen, B., Schultes, C. M., Hazel, P., Mann, J., & Neidle, S. (2004) · Organic & Biomolecular Chemistry · doi:10.1039/b316055f · Cited by 107
Chang, C., Sun, W. T., Cruz, A., Saitoh, M., Tai, M.-H., & Trosko, J. E. (2001) · Radiation Research · doi:10.1667/0033-7587(2001)155[0201:ahbect]2.0.co;2 · Cited by 106
Lanzendorf, S. E., Boyd, C. A., Wright, D. L., Muasher, S. J., Oehninger, S., & Hodgen, G. D. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)01825-8 · Cited by 106
Volonte, D., Zou, H., Bartholomew, J. N., Liu, Z., Morel, P. A., & Galbiati, F. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.598268 · Cited by 104
Hippocampal telomerase is involved in the modulation of depressive behaviors
Zhou, Q.-G., Hu, Y., Wu, D.-L., Zhu, L.-J., Chen, C., Jin, X., Luo, C.-X., Wu, H.-Y., Zhang, J., & Zhu, D.-Y. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0805-11.2011 · Cited by 105
“Telomeric repeat amplification protocol (TRAP) reactions were performed using the TRAPEZE XL telomerase detection kit (Millipore), following the manufacturer’s instructions.”
MethodInfluential
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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