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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
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 501–600 of 1,043
Fu, W., Killen, M. W., Culmsee, C., Dhar, S., Pandita, T. K., & Mattson, M. P. (2000) · Journal of Molecular Neuroscience · doi:10.1385/jmn:14:1-2:003 · Cited by 184
Custódio, M. R., Prokic, I., Steffen, R., Koziol, C., Borojević, R., Brümmer, F., Nickel, M., & Müller, W. E. G. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00078-5 · Cited by 185
InTERTpreting telomerase structure and function
Wyatt, H. D. M., West, S. C., & Beattie, T. L. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq370 · Cited by 190
“Telomerase activation is the most common pathway for cellular immortalization and transformation; at least 85% of human cancer cells constitutively express the telomerase catalytic subunit and utilize telomerase-dependent telomere elongation to attain unlimited growth potential (147).”
BackgroundN-Terminal Domains of the Human Telomerase Catalytic Subunit Required for Enzyme Activity in Vivo
Armbruster, B. N., Banik, S. S. R., Guo, C., Smith, A. C., & Counter, C. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.22.7775-7786.2001 · Cited by 183
“Normally, somatic cells express only the hTR subunit (2, 18), but during tumorigenesis the hTERT gene is illegitimately activated, restoring telomerase activity, preventing further telomere shortening and thereby immortalizing cells (14, 33 , 35, 41, 47, 48).”
Backgroundde Vitis, M., Berardinelli, F., & Sgura, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020606 · Cited by 182
“In humans, telomerase activity is known to be upregulated in those cells that need to maintain an active proliferative and renewal potential, such as embryonic stem cells and germ-line cells [12].”
BackgroundAlternative lengthening of telomeres: from molecular mechanisms to therapeutic outlooks
Zhang, J., & Zou, L. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00391-6 · Cited by 192
Sedivy, J. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9078 · Cited by 182
Chang, S., Khoo, C. M., Naylor, M. L., Maser, R. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1029903 · Cited by 183
Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells
Cao, Y., Bryan, T. M., & Reddel, R. R. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00815.x · Cited by 186
Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma
Ferber, M. J., Thorland, E. C., Brink, A. A. T. P., Rapp, A. K., Phillips, L. A., McGovern, R. M., Gostout, B. S., Cheung, T. H., Chung, T. K. H., FU, W. Y., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1207006 · Cited by 182
“In many tumors, this is via the activation of telomerase (Kim et al., 1994). hTERT expression is carefully regulated as it is the catalytic subunit of telomerase (Meyerson et al., 1997).”
BackgroundHuppert, J. L. (2008) · Biochimie · doi:10.1016/j.biochi.2008.01.014 · Cited by 189
Trophoblast 'pseudo-tumorigenesis': Significance and contributory factors
Soundararajan, R., & Rao, A. J. (2004) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-2-15 · Cited by 188
Telomerase Activity Is Sufficient To Allow Transformed Cells To Escape from Crisis
Halvorsen, T., Leibowitz, G., & Levine, F. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.3.1864 · Cited by 180
“The rare clones that do emerge from crisis invariably exhibit some form of telomere stabilization, usually by telomerase (25) but sometimes by alternate mechanisms (9), implying that telomere stabilization is crucial to continued growth.”
BackgroundEffects of hepatitis B virus X protein on the development of liver cancer
Zhang, X., Zhang, H., & Ye, L. (2006) · Journal of Laboratory and Clinical Medicine · doi:10.1016/j.lab.2005.10.003 · Cited by 181
Damle, R. N., Batliwalla, F., Ghiotto, F., Valetto, A., Albesiano, E., Sison, C. P., Allen, S. L., Kolitz, J. E., Vinciguerra, V. P., Kudalkar, P., et al. (2003) · Blood · doi:10.1182/blood-2003-04-1345 · Cited by 190
Alternative lengthening of telomeres is associated with chromosomal instability in osteosarcomas
Scheel, C., Schaefer, K., Jauch, A. S., Keller, M., Wai, D., Brinkschmidt, C., van Valen, F., Boecker, W., Dockhorn‐Dworniczak, B., & Poremba, C. (2001) · Oncogene · doi:10.1038/sj.onc.1204493 · Cited by 181
“Earlier investigations revealed telomerase activity (TA) in 90% of human tumors, but not in normal tissues (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundHou, M., Xu, D., Björkholm, M., & Gruber, A. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.3.519 · Cited by 175
“Unlike healthy cells, most malignant human cells are capable of escaping senescence and sustaining infinite proliferation through the activation of telomerase to stabilize their telomere length (1, 2).”
BackgroundKang, J. U., Koo, S. H., Kwon, K. C., Park, J. W., & Kim, J. (2008) · Cancer Genetics and Cytogenetics · doi:10.1016/j.cancergencyto.2007.12.004 · Cited by 180
Gertler, R., Rosenberg, R., Stricker, D., Friederichs, J., Hoos, A., Werner, M., Ulm, K., Holzmann, B., Nekarda, H., & Siewert, J.-R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.09.160 · Cited by 180
Zhang, Y., Toh, L.-L., Lau, P., & Wang, X. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.368282 · Cited by 185
“A high level of telomerase activity (TA)(2) is detected in about 90% of human cancer specimens, whereas most somatic cells do not display TA or express it only at very low levels in a cell cycle-dependent manner (5, 6).”
BackgroundMethodInfluentialClinical implications of telomerase in cancer
Kim, N. W. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00057-9 · Cited by 179
Self-citationWon, J., Yim, J., & Kim, T. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206064200 · Cited by 184
Telomerase gene mutations are associated with cirrhosis formation
Hartmann, D., Srivastava, U., Thaler, M., Kleinhans, K. N., N'Kontchou, G., Scheffold, A., Bauer, K., Kratzer, R. F., Kloos, N., Katz, S.-F., et al. (2011) · Hepatology · doi:10.1002/hep.24217 · Cited by 173
“However, telomeres shorten as a consequence of cell division due to the ‘‘end replication problem’’ of DNA polymerase, processing of telomeres during S-phase of cell cycle, and the absence of telomerase expression in most somatic tissues.(9) Telomere shortening limits the proliferative life span of human cells to 50-7…”
BackgroundMolecular Genetics and Epidemiology of Prostate Carcinoma
Ruijter, E., van de Kaa, C., Miller, G. J., Ruiter, D. J., Debruyne, F. M. J., & Schalken, J. A. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.1.0356 · Cited by 183
“Invertebrates,telomeresconsistof multipletandemrepeatsofthesequenceTTAGGG(270).”
BackgroundHypoxia Extends the Life Span of Vascular Smooth Muscle Cells through Telomerase Activation
Minamino, T., Mitsialis, S. A., & Kourembanas, S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3336-3342.2001 · Cited by 179
“High levels of telomerase activity are readily detected in cancer cells but not in most normal somatic cells, indicating that telomerase function is required for tumor growth (9).”
Wege, H., Le, H. T., Chui, M. S., Liu, L., Wu, J. H., Giri, R. K., Malhi, H., Sappal, B. S., Kumaran, V., Gupta, S. K., et al. (2003) · Gastroenterology · doi:10.1053/gast.2003.50064 · Cited by 177
DNA-PKcs is critical for telomere capping
Gilley, D. P., Tanaka, H., Hande, M. P., Kurimasa, A., Li, G. C., Oshimura, M., & Chen, D. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261574698 · Cited by 177
Telomerase Activity Concentrates in the Mitotically Active Segments of Human Hair Follicles
Ramirez, R. D., Wright, W. E., Shay, J. W., & Taylor, R. S. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12285654 · Cited by 174
Self-citationCharacteristics and Pathomechanisms of Endogenously Aged Skin
Makrantonaki, E., & Zouboulis, C. C. (2007) · Dermatology · doi:10.1159/000100890 · Cited by 184
Zhang, Z., Dai, J., Veliath, E., Jones, R. A., & Yang, D. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1029 · Cited by 183
“Telomerase is activated in 80–85% of human cancer cells and has been suggested to play a key role in maintaining the malignant phenotype by stabilizing telomere length and integrity (18,19).”
BackgroundParkinson, G. N., Cuenca, F., & Neidle, S. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.06.022 · Cited by 178
Niewisch, M. R., & Savage, S. A. (2019) · Expert Review of Hematology · doi:10.1080/17474086.2019.1662720 · Cited by 189
Telomere maintenance mechanisms and cellular immortalization
Colgin, L. M., & Reddel, R. R. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80014-8 · Cited by 177
The Catalytic Subunit of Telomerase Protects Neurons Against Amyloid β‐Peptide‐Induced Apoptosis
Zhu, H., Fu, W., & Mattson, M. P. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750117.x · Cited by 175
Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis
Miura, N., Horikawa, I., Nishimoto, A., Ohmura, H., Ito, H., Hirohashi, S., Shay, J. W., & Oshimura, M. (1997) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(96)00329-9 · Cited by 174
Self-citationYi, X., Tesmer, V. M., Savre‐Train, I., Shay, J. W., & Wright, W. E. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.3989 · Cited by 178
“Although telomerase is absent in most human adult somatic cells, telomerase activity is detected in most cancer cells (25).”
BackgroundSelf-citationDevelopment of adrenal cortex zonation
Xing, Y., Lerario, A. M., Rainey, W., & Hammer, G. D. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.02.001 · Cited by 174
“In order to expand its replicative potential, many cancers overexpress telomerase.(210) A recent study has shown that TERT, a gene that codes for the catalytic subunit of the telomerase enzyme, is frequently amplified in ACC.”
Chen, Z., Qin, Q., Qin, J.-L., Liu, Y., Huang, K.-B., Li, Y., Meng, T., Zhang, G., Peng, Y., Luo, X.-J., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm5012484 · Cited by 175
Chessells, J. M., Hall, E., Prentice, H. G., Durrant, J., Bailey, C. C., & Richards, S. M. (1998) · Leukemia · doi:10.1038/sj.leu.2400959 · Cited by 174
Kyo, S., & Inoue, M. (2002) · Oncogene · doi:10.1038/sj.onc.1205163 · Cited by 180
“This concept was supported by ®ndings that telomerase activity is observed in the vast majority of cancers or cancer cell lines but not in most normal tissues (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundShay, J. W. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.12.001 · Cited by 174
Min, J., Wright, W. E., & Shay, J. W. (2019) · Genes & Development · doi:10.1101/gad.324905.119 · Cited by 181
“Most cancers are of epithelial origin (carcinomas) and reactivate telomerase activity (Kim et al. 1994).”
BackgroundSelf-citationTargeting telomerase for cancer therapeutics
Shay, J. W., & Keith, W. N. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604209 · Cited by 171
“Telomerase is detected in approximately 90% of all malignant tumours (Kim et al, 1994; Shay and Bacchetti, 1997), making it a highly attractive target for the development of mechanism-based therapeutics (Keith et al, 2007).”
BackgroundSelf-citationNoncanonical Functions of Telomerase: Implications in Telomerase-Targeted Cancer Therapies
Li, Y., & Tergaonkar, V. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3568 · Cited by 180
Folding Pathways of Human Telomeric Type-1 and Type-2 G-Quadruplex Structures
Mashimo, T., Yagi, H., Sannohe, Y., Rajendran, A., & Sugiyama, H. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105806u · Cited by 171
DNA damage, mutation and fine structure DNA repair in aging
Bohr, V. A., & Anson, R. M. (1995) · Mutation Research/DNAging · doi:10.1016/0921-8734(95)00008-t · Cited by 173
Telomere maintenance by telomerase and by recombination can coexist in human cells
Cerone, M. A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.18.1945 · Cited by 173
“Telomerase activity was assayed by TRAP (29) at different PDs and was found to persist in all populations reconstituted for the enzyme (Fig.”
MethodInfluentialRequirement for p27KIP1 in Retinoblastoma Protein-Mediated Senescence
Alexander, K., & Hinds, P. W. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3616-3631.2001 · Cited by 164
White, L. K., Wright, W. E., & Shay, J. W. (2001) · Trends in biotechnology · doi:10.1016/s0167-7799(00)01541-9 · Cited by 171
Self-citationStop pulling my strings — what telomeres taught us about the DNA damage response
Denchi, E. L., & Sfeir, A. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.43 · Cited by 177
Cellular delivery of peptide nucleic acids and inhibition of human telomerase
Hamilton, S. E., Simmons, C. G., Kathiriya, I. S., & Corey, D. R. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80046-5 · Cited by 171
Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation
Kondo, S., Tanaka, Y., Kondo, Y., Hitomi, M., Barnett, G. H., Ishizaka, Y., Liu, J., Haqqi, T., Nishiyama, A., Villeponteau, B., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.10.801 · Cited by 170
TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma
Remke, M., Ramaswamy, V., Peacock, J., Shih, D. J. H., Koelsche, C., Northcott, P. A., Hill, N., Cavalli, F. M. G., Kool, M., Wang, X., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1198-2 · Cited by 164
“Telomere maintenance is fundamentally important to normal self-renewing stem cells and cancer cells [3, 7, 9, 14, 22].”
BackgroundThe molecular genetics of the telomere biology disorders
Bertuch, A. A. (2015) · RNA Biology · doi:10.1080/15476286.2015.1094596 · Cited by 173
“Some studies have used the telomerase repeat amplification protocol (TRAP) assay, which includes a polymerase chain reaction (PCR) step to amplify telomerase extended oligonucleotides.(11) However, because the PCR amplification step includes a primer that can anneal to any of the repetitive telomeric repeats that are…”
MethodThe Emerging Roles of TERRA in Telomere Maintenance and Genome Stability
Bettin, N., Pegorar, C. O., & Cusanelli, E. (2019) · Cells · doi:10.3390/cells8030246 · Cited by 169
“Accordingly, 90% of human cancers reactivate telomerase in order to maintain telomere length and attain unlimited proliferative capacity [46].”
BackgroundWei, S., Wei, S., & Sedivy, J. M. (1999) · PubMed · Cited by 166
Behaviour of Telomere and Telomerase during Aging and Regeneration in Zebrafish
Anchelin, M., Murcia, L., Alcaraz‐Pérez, F., García-Navarro, E. M., & Cayuela, M. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016955 · Cited by 174
“and it is highly detectable in immortalized cells and many tumour cell tissues”
BackgroundAlternative Lengthening of Telomeres: DNA Repair Pathways Converge
Sobinoff, A. P., & Pickett, H. A. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.09.003 · Cited by 177
Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics
Seimiya, H., Muramatsu, Y., Ohishi, T., & Tsuruo, T. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.021 · Cited by 168
Spontaneous regression of cancer
Papac, R. J. (1996) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(96)90023-7 · Cited by 168
“In a survey of 12 tumour tissue types, 90 of 101 were positive for telomerase activity (186).”
BackgroundXu, S., He, M. Y., Yu, H., Cai, X., Tan, X., Lü, B., & Shu, B. (2001) · Analytical Biochemistry · doi:10.1006/abio.2001.5418 · Cited by 167
Refining the telomere-telomerase hypothesis of aging and cancer
Holt, S. E., Shay, J. W., & Wright, W. E. (1996) · Nature Biotechnology · doi:10.1038/nbt0796-836 · Cited by 168
Self-citationNovel Nanosensors for Rapid Analysis of Telomerase Activity
Grimm, J., Pérez, J. M. S., Josephson, L., & Weissleder, R. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2798 · Cited by 167
“and not to primer Ts [5 -AAT-CCG-TCG-AGC-AGA-GTT (6)].”
BackgroundLack of cell cycle regulation of telomerase activity in human cells
Holt, S. E., Aisner, D. L., Shay, J. W., & Wright, W. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10687 · Cited by 166
Self-citationWang, W., Li, J., Rui, K., Gai, P., Zhang, J., & Zhu, J. (2015) · Analytical Chemistry · doi:10.1021/ac504652e · Cited by 164
Telomeres, telomerase and cancer: an up-date
Dhaene, K., Marck, E. V., & Parwaresch, R. M. (2000) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280000189 · Cited by 166
“variety of normal, benign, pre-malignant and malignant tissue specimens (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, and Table 13) [51].”
Ramachandran, C., Fonseca, H. B., Jhabvala, P., Escalon, E., & Melnick, S. J. (2002) · Cancer Letters · doi:10.1016/s0304-3835(02)00192-1 · Cited by 165
McMurray, H. R., & McCance, D. J. (2003) · Journal of Virology · doi:10.1128/jvi.77.18.9852-9861.2003 · Cited by 171
“One hundred nanograms of Gal4-luc was cotransfected with 100 ng of vector or p300 (1-743)-Gal4 fusion protein and 100 ng of DN Myc.”
MethodTelomerase and cancer: revisiting the telomere hypothesis
Autexier, C., & Greider, C. W. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10042-6 · Cited by 178
The disparity between human cell senescence in vitro and lifelong replication in vivo
Rubin, H. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-675 · Cited by 171
“Telomerase and telomere length in tissues, tumors, and cell lines Early studies indicated that there was no telomerase activity in somatic tissues, although such activity was detectable in germinal cell”
BackgroundRegulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase
Kharbanda, S. M., Kumar, V., Dhar, S., Pandey, P., Chen, C., Majumder, P. K., Yuan, Z.-M., Whang, Y. E., Strauss, W. M., Pandita, T. K., et al. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00483-8 · Cited by 170
“Other studies have shown that telomerase activity is detectable in human tumors [10,20,21].”
Grobelny, J. V., Godwin, A. K., & Broccoli, D. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.24.4577 · Cited by 168
Accelerated Telomere Shortening in Fibroblasts After Extended Periods of Confluency
Sitte, N. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00363-8 · Cited by 162
The Role of Telomere Biology in Cancer
Xu, L., Li, S., & Stohr, B. A. (2013) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164030 · Cited by 160
Tockman, M. S., Mulshine, J. L., Piantadosi, S., Erozan, Y. S., Gupta, P. K., Ruckdeschel, J. C., Taylor, P. R., Zhukov, T., Zhou, W., Qiao, Y., et al. (1997) · PubMed · Cited by 163
HPV-mediated transformation of the anogenital tract
Steenbergen, R. D. M., de Wilde, J., Wilting, S. M., Brink, A. A. T. P., Snijders, P. J. F., & Meijer, C. J. L. M. (2005) · Journal of Clinical Virology · doi:10.1016/j.jcv.2004.11.019 · Cited by 159
Human telomerase contains two cooperating telomerase RNA molecules
Wenz, C., Enenkel, B., Amacker, M., Kelleher, C., Damm, K., & Lingner, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.13.3526 · Cited by 163
Characterization and developmental patterns of telomerase expression in plants
Fitzgerald, M. S., McKnight, T. D., & Shippen, D. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14422 · Cited by 162
A critical stem-loop structure in the CR4-CR5 domain of mammalian telomerase RNA
Chen, J. J. ‐. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.2.592 · Cited by 162
“(20) or the TRAPEZE Telomerase Detection Kit from Intergen.”
MethodHuman telomerase inhibition by substituted acridine derivatives
Harrison, R. J., Gowan, S. M., Kèlland, L. R., & Neidle, S. (1999) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(99)00394-7 · Cited by 164
Hiyama, E., Hiyama, K., Yokoyama, T., & Shay, J. W. (2001) · Neoplasia · doi:10.1038/sj.neo.7900134 · Cited by 165
Self-citationMolecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation
Rubio, D., García, S., Paz, M. F., de la Cueva, T., López-Fernández, L. A., Lloyd, A. C., Garcı́a-Castro, J., & Bernad, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001398 · Cited by 166
“Telomerase activity has been found in almost all human tumors but not in adjacent normal cells [21] and maintenance of telomere stability is required for the long-term proliferation of tumor cells [22].”
BackgroundRoumelioti, F., Sotiriou, S. K., Katsini, V., Chiourea, M., Halazonetis, T. D., & Gagos, S. (2016) · EMBO Reports · doi:10.15252/embr.201643169 · Cited by 170
Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway
Chen, Y., Shen, Y., Hsia, H.-Y., Tiang, Y. P., Sung, T.-L., & Chen, L. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3498 · Cited by 168
Burns, J. S., Abdallah, B. M., Guldberg, P., Rygaard, J., Schrøder, H. D., & Kassem, M. S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2218 · Cited by 163
“prepared using a 1 CHAPS lysis method (29).”
MethodThe genetics of dyskeratosis congenita
Mason, P. J., & Bessler, M. (2011) · Cancer Genetics · doi:10.1016/j.cancergen.2011.11.002 · Cited by 167
“Curiously TERC is widely expressed while TERT expression in humans is restricted to embryonic cells, stem cells, lymphocytes, and cancer cells(45, 46).”
BackgroundCancer risk related to mammary gland structure and development
Russo, J., Hu, Y. F., da Silva, I. D. C. G., & Russo, I. H. (2001) · Microscopy Research and Technique · doi:10.1002/1097-0029(20010115)52:2 · Cited by 161
Telomerase in the early detection of cancer.
Shay, J. W., & Gazdar, A. F. (1997) · Journal of Clinical Pathology · doi:10.1136/jcp.50.2.106 · Cited by 162
Self-citationSevere growth defect in mouse cells lacking the telomerase RNA component
Niida, H., Matsumoto, T., Satoh, H., Shiwa, M., Tokutake, Y., Furuichi, Y., & Shinkai, Y. (1998) · Nature Genetics · doi:10.1038/580 · Cited by 156
Brunsvig, P. F., Kyte, J. A., Kersten, C., Sundstrøm, S. H., Møller, M., Nyakas, M., Hansen, G. L., Gaudernack, G., & Aamdal, S. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1385 · Cited by 159
“The enzyme telomerase is expressed in most human cancers, including NSCLC (7, 8) and is considered as an attractive target for a universal cancer vaccine (9-14).”
BackgroundListerman, I., Sun, J., Gazzaniga, F. S., Lukas, J. L., & Blackburn, E. H. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3082 · Cited by 162
Telomere attrition as ageing biomarker.
Bekaert, S., Meyer, T. D., & Oostveldt, P. V. (2005) · PubMed · Cited by 158
Telomere-associated aging disorders
Opresko, P. L., & Shay, J. W. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.009 · Cited by 162
Self-citationHeparanase and the hallmarks of cancer
Jayatilleke, K. M., & Hulett, M. D. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02624-1 · Cited by 167
Wu, Z., Guo, Q., You, Q., Zhao, L., & Gu, H.-Y. (2004) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.27.1769 · Cited by 158
Ng, L. J., Cropley, J. E., Pickett, H. A., Reddel, R. R., & Suter, C. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn1030 · Cited by 176
“In around 85% of tumours, telomere length maintenance is achieved by activation of telomerase (6); telomerase activity is not detectable or present at very low levels in most normal human somatic cells (3).”
BackgroundMethodPullamsetti, S. S., Savai, R., Seeger, W., & Goncharova, E. A. (2016) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201606-1226pp · Cited by 158
Short Telomere Length and Breast Cancer Risk: A Study in Sister Sets
Shen, J., Terry, M. B., Gurvich, I., Liao, Y., Senie, R. T., & Santella, R. M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3490 · Cited by 157
“Many previous experiments showed that tumor cells have extremely short and stable telomeres, and their stability is achieved by the activation of telomerase (33, 34).”
BackgroundLi, S., Crothers, J., Haqq, C. M., & Blackburn, E. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502782200 · Cited by 160
Incles, C. M., Schultes, C. M., Kempski, H. M., Koehler, H., Kèlland, L. R., & Neidle, S. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1201.3.10 · Cited by 163
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review