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
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
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Self-citationGold Nanoparticles in Chemical and Biological Sensing
Saha, K., Agasti, S. S., Kim, C., Li, X., & Rotello, V. M. (2012) · Chemical Reviews · doi:10.1021/cr2001178 · Cited by 4,637
A survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794
Self-citationMultiplexed electrical detection of cancer markers with nanowire sensor arrays
Zheng, G., Patolsky, F., Cui, Y., Wang, W. U., & Lieber, C. M. (2005) · Nature Biotechnology · doi:10.1038/nbt1138 · Cited by 2,461
“Telomerase activity has been found in at least 80% of all known human cancer”
BackgroundCreation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256
Self-citationThe RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Self-citationTelomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Feeder-free growth of undifferentiated human embryonic stem cells
Xu, C., Inokuma, M. S., Denham, J., Golds, K., Kundu, P., Gold, J. D., & Carpenter, M. K. (2001) · Nature Biotechnology · doi:10.1038/nbt1001-971 · Cited by 1,872
Fraietta, J. A., Lacey, S. F., Orlando, E. J., Pruteanu-Malinici, I., Gohil, M., Lundh, S., Boesteanu, A. C., Wang, Y., O’Connor, R. S., Hwang, W.-T., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0010-1 · Cited by 1,785
How Shelterin Protects Mammalian Telomeres
Palm, W., & de Lange, T. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130350 · Cited by 1,802
Fetal cell microchimerism in tissue from multiple sites in women with systemic sclerosis
Johnson, K. L., Nelson, J. L., Fürst, D. E., McSweeney, P. A., Roberts, D. J., Zhen, D., & Bianchi, D. W. (2001) · Arthritis & Rheumatism · doi:10.1002/1529-0131(200108)44:8 · Cited by 173
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784
“TRAP telomerase assay (Kim et al., 1994), two mortal fibroblast strains, WI-38 and IMR-90, were found to lack detectable telomerase activity, in contrast to three im-hEST2 Expression in Primary Human Cancers The expression of hEST2 mRNA in cancer cell lines sug- mortal cell lines, HeLa, 293, and…”
InfluentialTRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709
Ingram, D. A., Mead, L. E., Tanaka, H., Meade, V. M., Fenoglio, A., Mortell, K. E., Pollok, K. E., Ferkowicz, M. J., Gilley, D. P., & Yöder, M. C. (2004) · Blood · doi:10.1182/blood-2004-04-1396 · Cited by 1,534
Amit, M., Carpenter, M. K., Inokuma, M. S., Chiu, C., Harris, C. P., Waknitz, M. A., Itskovitz‐Eldor, J., & Thomson, J. A. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9912 · Cited by 1,471
Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H., Gallia, G. L., Giovanella, B. C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303607110 · Cited by 1,368
Telomere elongation in immortal human cells without detectable telomerase activity
Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., & Reddel, R. R. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00098.x · Cited by 1,279
Bryan, T. M., Englezou, A., Dalla-Pozza, L., Dunham, M. A., & Reddel, R. R. (1997) · Nature Medicine · doi:10.1038/nm1197-1271 · Cited by 1,292
Essential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270
“From this crisis period, immortal cells emerge that have reactivated telomerase and maintain stable telomere structure”
BackgroundCancer biomarker detection: recent achievements and challenges
Wu, L. J., & Qu, X. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00370e · Cited by 1,252
Control of telomere length by the human telomeric protein TRF1
van Steensel, B., & de Lange, T. (1997) · Nature · doi:10.1038/385740a0 · Cited by 1,219
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206
“The telomere repeat amplification protocol (TRAP) assay was performed with several modifications to the original protoco”
MethodA telomerase component is defective in the human disease dyskeratosis congenita
Mitchell, J. R., Wood, E., & Collins, K. (1999) · Nature · doi:10.1038/990141 · Cited by 1,168
The Biology of Cancer Stem Cells
Lobo, N. A., Shimono, Y., Qian, D., & Clarke, M. F. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104154 · Cited by 1,070
“Telomerase, an enzyme that adds terminal repeats to the end of telomeres, is expressed at high levels in normal self-renewing blood cell populations (Allsopp et al. 2003, Morrison et al. 1996) and tumor cell populations (Kim et al. 1994).”
BackgroundInhibition of telomerase limits the growth of human cancer cells
Hahn, W. C., Stewart, S. A., Brooks, M. W., York, S. G., Eaton, E. N., Kurachi, A. L., Beijersbergen, R. L., Knoll, J. H. M., Meyerson, M. M., & Weinberg, R. A. (1999) · Nature Medicine · doi:10.1038/13495 · Cited by 1,038
Gronthos, S., Zannettino, A. C. W., Hay, S. J., Shi, S., Graves, S. E., Kortesidis, A., & Simmons, P. J. (2003) · Journal of Cell Science · doi:10.1242/jcs.00369 · Cited by 1,025
Vaziri, H., & Benchimol, S. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70109-5 · Cited by 1,003
“[6–8].”
Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging
Blackburn, E. H., Greider, C. W., & Szostak, J. W. (2006) · Nature Medicine · doi:10.1038/nm1006-1133 · Cited by 880
“The subsequent demonstration that telomerase is active in many human tumor cells but is not detectable in most normal tissues further strengthened the idea that telomerase inhibition might be an effective way to kill cancer cell”
BackgroundChin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979
The common biology of cancer and ageing
Finkel, T., Serrano, M., & Blasco, M. A. (2007) · Nature · doi:10.1038/nature05985 · Cited by 988
Armanios, M., & Blackburn, E. H. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3246 · Cited by 982
Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules
Labib, M., Sargent, E. H., & Kelley, S. O. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00220 · Cited by 994
Multilineage differentiation from human embryonic stem cell lines
Odorico, J. S., Kaufman, D. S., & Thomson, J. A. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-193 · Cited by 969
“The expression of telomerase, a ribonucleoprotein that adds telomere repeats to chromosome ends, thereby maintaining their length, is highly correlated with immortality in human cell lines [ 19 ].”
BackgroundWeinrich, S. L., Pruzan, R., Ma, L., Ouellette, M. M., Tesmer, V. M., Holt, S. E., Bodnar, A. G., Lichtsteiner, S., Kim, N. W., Trager, J. B., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-498 · Cited by 975
Self-citationGenomic and Epigenetic Instability in Colorectal Cancer Pathogenesis
Grady, W. M., & Carethers, J. M. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.076 · Cited by 991
Telomeres and telomerase: three decades of progress
Shay, J. W., & Wright, W. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0099-1 · Cited by 924
Self-citationDePinho, R. A. (2000) · Nature · doi:10.1038/35041694 · Cited by 951
Rules for Making Human Tumor Cells
Hahn, W. C., & Weinberg, R. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmra021902 · Cited by 951
Modelling the molecular circuitry of cancer
Hahn, W. C., & Weinberg, R. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc795 · Cited by 953
“Most (85–90%) of these tumour cells succeed in doing so by acquiring expression of telomerase, which is a reverse transcriptase that extends telomeric DN”
BackgroundHuman Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898
“Since first discovered in Tetrahymena thermophila in 1985 (82), telomerase activity was found to be absent in most normal human somatic cells but present in over 90% of cancerous cells and in vitro-immortalized cells (124, 210).”
BackgroundMethodInfluentialSelf-citationMakarov, V. L., Hirose, Y., & Langmore, J. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81908-x · Cited by 959
Direct activation of TERT transcription by c-MYC
Wu, K.-J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., & Dalla-Favera, R. (1999) · Nature Genetics · doi:10.1038/6010 · Cited by 893
“Contrary to early reports suggesting a specific association between telomerase activity and cell immortalization or transformatio”
BackgroundSemiconductor Quantum Dots for Bioanalysis
Gill, R., Zayats, M., & Willner, I. (2008) · Angewandte Chemie International Edition · doi:10.1002/anie.200800169 · Cited by 901
Patel, D. J., Phan, A. T., & Kuryavyi, V. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm711 · Cited by 892
“By contrast, telomeric overhangs can be elongated by the enzyme telomerase, a ribonucleoprotein complex with reverse transcriptase activity (83), which is expressed in the majority of cancer cells, thereby helping to maintain telomere length (84).”
BackgroundHeterogeneity in telomere length of human chromosomes
Lansdorp, P. M. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.5.685 · Cited by 886
“Telomere shortening may act as a mitotic clock in normal somatic cells ( 9) and high levels of the enzyme telomerase (capable of elongating telomeres) have been found in tumor cells (10).”
BackgroundTelomeres: Beginning to Understand the End
Zakian, V. A. (1995) · Science · doi:10.1126/science.270.5242.1601 · Cited by 859
Telomerase activation by the E6 gene product of human papillomavirus type 16
Klingelhutz, A. J., Foster, S. A., & McDougall, J. K. (1996) · Nature · doi:10.1038/380079a0 · Cited by 841
Structure of the Human Telomere in K + Solution: An Intramolecular (3 + 1) G-Quadruplex Scaffold
Luu, K. N., Phan, A. T., Kuryavyi, V., Lacroix, L., & Patel, D. J. (2006) · Journal of the American Chemical Society · doi:10.1021/ja062791w · Cited by 814
From polyploidy to aneuploidy, genome instability and cancer
Štorchová, Z., & Pellman, D. S. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1276 · Cited by 822
Senescence and aging: the critical roles of p53
Rufini, A., Tucci, P., Celardo, I., & Melino, G. (2013) · Oncogene · doi:10.1038/onc.2012.640 · Cited by 798
Bypass of Senescence After Disruption of p21 CIP1/WAF1 Gene in Normal Diploid Human Fibroblasts
Brown, J. P., Wei, W., & Sedivy, J. M. (1997) · Science · doi:10.1126/science.277.5327.831 · Cited by 804
Regulation of Telomerase by Telomeric Proteins
Smogorzewska, A., & de Lange, T. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.071403.160049 · Cited by 813
A hitchhiker's guide to G-quadruplex ligands
Monchaud, D., & Teulade‐Fichou, M. (2007) · Organic & Biomolecular Chemistry · doi:10.1039/b714772b · Cited by 808
Telomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745
Control of Human Telomere Length by TRF1 and TRF2
Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S., Schaefer, M. R., Schnapp, G., & de Lange, T. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1659-1668.2000 · Cited by 768
“pared by digesting pGRN78 (25) with XbaI, and the b-actin probe was obtained”
MethodHayflick, his limit, and cellular ageing
Shay, J. W., & Wright, W. E. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036093 · Cited by 764
Self-citationTelomerase activity in normal and malignant hematopoietic cells.
Broccoli, D., Young, J. W., & de Lange, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9082 · Cited by 754
Telomerase maintains telomere structure in normal human cells
Kenichi, M., Yu, E. Y., Shilagardi, K., Ben‐Porath, I., Currier, J. L., Metz, G. B., Brooks, M. W., Kaneko, S., Seishi, M., DeCaprio, J. A., et al. (2006) · Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) · Cited by 738
Senescence and immortalization: role of telomeres and telomerase
Shay, J. W., & Wright, W. E. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh296 · Cited by 747
Self-citationTelomerase and cancer therapeutics
Harley, C. B. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2275 · Cited by 728
Self-citationDifferences between human and mouse embryonic stem cells
Ginis, I., Luo, Y., Miura, T., Thies, S., Brandenberger, R., Gerecht, S., Amit, M., Höke, A., Carpenter, M. K., Itskovitz‐Eldor, J., et al. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2003.12.034 · Cited by 724
“Telomerase was measured using the telomeric repeat amplification protocol (TRAP) assay as described (Kim et al., 1994; Weinrich et al., 1997), Terminal restriction fragment (TRF) size was determined using Southern hybridization as described (Allsopp et al.”
MethodRoles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies
Jafri, M. A., Ansari, S. A., Alqahtani, M. H., & Shay, J. W. (2016) · Genome Medicine · doi:10.1186/s13073-016-0324-x · Cited by 716
“telomerase activity in ~90 % of human cancers and cell lines [89], and in 1998 the same team demonstrated that introduction of hTERT”
Self-citationMcEachern, M. J., Krauskopf, A., & Blackburn, E. H. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.331 · Cited by 716
Mohanty, J., Barooah, N., Dhamodharan, V., Harikrishna, S., Pradeepkumar, P. I., & Bhasikuttan, A. C. (2012) · Journal of the American Chemical Society · doi:10.1021/ja309588h · Cited by 700
Blechacz, B. R. A., & Gores, G. J. (2008) · Hepatology · doi:10.1002/hep.22310 · Cited by 703
Chong, L., van Steensel, B., Broccoli, D., Erdjument‐Bromage, H., Hanish, J., Tempst, P., & de Lange, T. (1995) · Science · doi:10.1126/science.270.5242.1663 · Cited by 714
Bernardo, M. E., Zaffaroni, N., Novara, F., Cometa, A. M., Avanzini, M. A., Moretta, A., Montagna, D., Maccario, R., Villa, R., Daidone, M. G., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4690 · Cited by 708
Developmental and tissue-specific regulation of mouse telomerase and telomere length.
Prowse, K. R., & Greider, C. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.11.4818 · Cited by 697
Self-citationRole of Telomeres and Telomerase in Aging and Cancer
Shay, J. W. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0062 · Cited by 668
“Nearly the complete spectrum of human tumor types has been shown to be telomerase-positive (2, 3).”
InfluentialSelf-citationKim, N. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.13.2595 · Cited by 688
Self-citationYeager, T. R., Neumann, A. A., Englezou, A., Huschtscha, L. I., Noble, J. R., & Reddel, R. R. (1999) · PubMed · Cited by 680
Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization
Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., & Weinberg, R. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14723 · Cited by 649
Alternative lengthening of telomeres in mammalian cells
Henson, J. D., Neumann, A. A., Yeager, T. R., & Reddel, R. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205058 · Cited by 684
A Mammalian Telomerase-Associated Protein
Harrington, L. A., McPhail, T., Mar, V. L., Zhou, W., Oulton, R., Program, A. E., Bass, M. B., Arruda, I., & Robinson, M. O. (1997) · Science · doi:10.1126/science.275.5302.973 · Cited by 661
Nunes, M. C., Roy, N. S., Keyoung, H. M., Goodman, R. R., McKhann, G. M., Jiang, L., Kang, J., Nedergaard, M., & Goldman, S. A. (2003) · Nature Medicine · doi:10.1038/nm837 · Cited by 659
Myc activates telomerasePreprint
Wang, J., Xie, L. Y., Allan, S., Beach, D., & Hannon, G. J. (1998) · Genes & Development · doi:10.1101/gad.12.12.1769 · Cited by 658
Immortalization of Human Bronchial Epithelial Cells in the Absence of Viral Oncoproteins
Ramirez, R., Sheridan, S., Girard, L., Sato, M., Kim, Y., Pollack, J., Peyton, M., Zou, Y. S., Kurie, J., Dimaio, J. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-3703 · Cited by 666
Self-citation5'-UTR RNA G-quadruplexes: translation regulation and targeting
Bugaut, A., & Balasubramanian, S. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks068 · Cited by 654
“Owing to the strong associations between telomerase over-expression and human cancers (8), extensive research effort has been devoted to investigate the relevance of G-quadruplex formation in telomere maintenance (9,10).”
BackgroundMolecular Biology of Neuroblastoma
Maris, J. M., & Matthay, K. K. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.7.2264 · Cited by 634
Telomere maintenance as a target for anticancer drug discovery
Neidle, S., & Parkinson, G. N. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd793 · Cited by 631
Chronic myeloid leukaemia as a model of disease evolution in human cancer
Melo, J. V., & Barnes, D. J. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2147 · Cited by 629
“Paradoxically, telomerase activity has been described as being upregulated in many human cancers, and active telomerase is thought to be essential for the immortalization of malignant cell”
BackgroundCisplatin: From DNA damage to cancer chemotherapy
Cohen, S. M., & Lippard, S. J. (2001) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(01)67026-0 · Cited by 614
Correlating telomerase activity levels with human neuroblastoma outcomes
Hiyama, E., Hiyama, K., Yokoyama, T., Matsuura, Y., Piatyszek, M. A., & Shay, J. W. (1995) · Nature Medicine · doi:10.1038/nm0395-249 · Cited by 611
Self-citationEnumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation
Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., DeCaprio, J. A., & Weinberg, R. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2111-2123.2002 · Cited by 626
“cells to transformation by oncogenes derive, in part, from the constitutive expression of telomerase, the enzyme that maintains telomeres, in rodent but not in human cells (33, 59).”
BackgroundTelomerase activity in normal leukocytes and in hematologic malignancies
Counter, C. M., Gupta, J., Harley, C., Leber, B. F., & Bacchetti, S. (1995) · Blood · doi:10.1182/blood.v85.9.2315.bloodjournal8592315 · Cited by 604
Self-citationTelomerase in the human organism
Collins, K., & Mitchell, J. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205083 · Cited by 616
“The vast majority of human cancers and cancer cell lines possess active telomerase and maintain stable telomeres with proliferation (Kim et al., 1994; reviewed by Shay and Bacchetti, 1997).”
BackgroundTelomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas
Nakayama, J., Tahara, H., 栄治, 田., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Nakanishi, E., Ide, T., & Ishikawa, F. (1998) · Nature Genetics · doi:10.1038/ng0198-65 · Cited by 605
Cdc13p: A Single-Strand Telomeric DNA-Binding Protein with a Dual Role in Yeast Telomere Maintenance
Nugent, C. I., Hughes, T., Lue, N. F., & Lundblad, V. (1996) · Science · doi:10.1126/science.274.5285.249 · Cited by 606
Petersen, G. M., Amundadottir, L. T., Fuchs, C. S., Kraft, P. L., Stolzenberg‐Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M. D., et al. (2010) · Nature Genetics · doi:10.1038/ng.522 · Cited by 598
“Although telomerase activity cannot be detected in most normal tissues, it is seen in approximately 90% of human cancer”
BackgroundThe application of DNA and RNA G-quadruplexes to therapeutic medicines
Collie, G. W., & Parkinson, G. N. (2011) · Chemical Society Reviews · doi:10.1039/c1cs15067g · Cited by 596
Burger, A. M., Dai, F., Schultes, C. M., Reszka, A. P., Moore, M. J., Double, J. A., & Neidle, S. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2910 · Cited by 609
“The integrity of human telomeric DNA is maintained in the overwhelming majority of tumor cells by the telomerase enzyme complex (1), in contrast to the progressive attrition of telomere length in most normal somatic cells that occurs as a consequence of the end replication effect (2).”
BackgroundG-quadruplex nucleic acids as therapeutic targets
Balasubramanian, S., & Neidle, S. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.04.637 · Cited by 594
“Interest in telomeres and telomerase as therapeutic targets arose following the seminal finding that telomerase is expressed in ca 80–85% of cancer cells and primary tumours, but not in normal somatic cells [43].”
BackgroundCommon genetic variation drives molecular heterogeneity in human iPSCs
Kilpinen, H., Goncalves, A., Leha, A., Afzal, V., Alasoo, K., Ashford, S., Bala, S., Bensaddek, D., Casale, F. P., Culley, O. J., et al. (2017) · Nature · doi:10.1038/nature22403 · Cited by 586
Kilian, A., Bowtell, D. D. L., Abud, H. E., Hime, G. R., Venter, D. J., Keese, P., Duncan, E. L., Reddel, R. R., & Jefferson, R. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.12.2011 · Cited by 592
“Not all immortalized cell lines contain detectable telomerase activity, however (16,20,23).”
BackgroundQuadruplex Nucleic Acids as Novel Therapeutic Targets
Neidle, S. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01835 · Cited by 587
Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance
Dalleau, S., Baradat, M., Guéraud, F., & Huc, L. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.138 · Cited by 580
“Telomerase activity is reported to be reactivated during carcinogenesis and cancer cells escape senescence.(126) It is well-described that oxidative stress accelerates telomere loss due to a decrease in telomerase activity in vitro.”
BackgroundIngram, D. A., Mead, L. E., Moore, D. B., Woodard, W., Fenoglio, A., & Yöder, M. C. (2004) · Blood · doi:10.1182/blood-2004-08-3057 · Cited by 582
Targeting telomeres and telomerase
Cian, A. D., Lacroix, L., Douarre, C., Temime‐Smaali, N., Trentesaux, C., Riou, J., & Mergny, J. (2007) · Biochimie · doi:10.1016/j.biochi.2007.07.011 · Cited by 583
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
