The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Abstract
Synthesis of DNA at chromosome ends by telomerase may be necessary for indefinite proliferation of human cells. A highly sensitive assay for measuring telomerase activity was developed. In cultured cells representing 18 different human tissues, 98 of 100 immortal and none of 22 mortal populations were positive for telomerase. Similarly, 90 of 101 biopsies representing 12 human tumor types and none of 50 normal somatic tissues were positive. Normal ovaries and testes were positive, but benign tumors such as fibroids were negative. Thus, telomerase appears to be stringently repressed in normal human somatic tissues but reactivated in cancer, where immortal cells are likely required to maintain tumor growth.
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In the citing paper
“Furthermore, although most human cancers (~90%) escape telomere crisis by activating telomerase56, a significant minority of cancers use an alternative telomere maintenance system, referred to as alternative lengthening of telomeres (ALT)161.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [56]
In the citing paper
“The notion that telomere function may indeed be required for immortalization is supported by the frequent activation of telomerase or ALT in human cancers (Kim et al. 1994; Bryan et al. 1995”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Kim et al. 1994
In the citing paper
“Telomerase activation is observed in approximately 90% of human cancers, irrespective of tumor type, while most normal tissues contain inactivated telomerase.(1)”
From Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [1]
In the citing paper
“This idea is consistent with the fact that telomerase activity is upregulated in most human cancers, which probably contributes to sustaining their immortality7.”
From The telomere syndromes (2012) · cites this paper as [7]
In the citing paper
“Virally transformed human cells that eliminate p53 and/or pRB function can escape crisis at very low frequencies, and invariably adopt telomere-maintenance programs: 80-90% of human tumors possess some telomerase activity, while the remainder maintain telomeres via a recombination-mediated process termed ALT (for Alternative Lengthening of Telomeres)37-40.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [38]
In the citing paper
“Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“In cancer cells, the reactivation of telomerase is thought to stabilize telomere length, thereby compensating for the cell division-related telomere erosion and providing unlimited proliferative capacity to malignant cells (Counter et al., 1992;Kim et al., 1994).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase activity has been demonstrated in immortalized cell lines and in 80±90% of human cancer specimens representing a range of cancer types (Counter et al., 1994;Kim et al., 1994;Shay and Bacchetti, 1997)”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Kim et al., 1994
In the citing paper
“Telomerase activity has been found in almost all human tumors but not in adjacent normal cells (3, 4).”
From Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death (1999) · cites this paper as [3]
In the citing paper
“Over the last decade it has become clear that most human cancers activate telomerase at some point during tumorigenesis, while this activity is largely absent in most normal tissues 70, 71 .”
From The common biology of cancer and ageing (2007) · cites this paper as [70]
Citations
Cites
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Self-citationStructure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M. A. C., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L., & Wu, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.18.6622 · Cited by 2,326
Telomere length predicts replicative capacity of human fibroblasts.
Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., & Harley, C. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10114 · Cited by 2,200
Self-citationCounter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096
Self-citationOlovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis
Greider, C. W., & Blackburn, E. H. (1989) · Nature · doi:10.1038/337331a0 · Cited by 1,643
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495
Flagged first, then by citations
Research works printed but not linked: 2
- GARNICK, M.B., THE DILEMMAS OF PROSTATE-CANCER, SCIENTIFIC AMERICAN 270: 72 (1994).
- WATSON, J. D., NATURE-NEW BIOLOGY 239: 197 (1972).
Cited by
Sorted by citations
Items 201–300 of 1,043
Functional Characterization and Developmental Regulation of Mouse Telomerase RNA
Blasco, M. A., Funk, W. D., Villeponteau, B., & Greider, C. W. (1995) · Science · doi:10.1126/science.7544492 · Cited by 364
Regulation of Telomerase Activity in Immortal Cell Lines
Holt, S. E., Wright, W. E., & Shay, J. W. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.2932 · Cited by 361
“Telomerase activity was measured by the TRAP assay (16, 23) as modified by Wright et al.”
Self-citationLong‐term culture of human embryonic stem cells in feeder‐free conditions
Rosler, E. S., Fisk, G. J., Ares, X., Irving, J., Miura, T., Rao, M. S., & Carpenter, M. K. (2003) · Developmental Dynamics · doi:10.1002/dvdy.10430 · Cited by 357
“Telomerase activity was measured using the TRAP assay as described (Kim et al., 1994; Weinrich et al., 1997).”
MethodHistorical claims and current interpretations of replicative aging
Wright, W. E., & Shay, J. W. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-682 · Cited by 355
“The need to overcome this limitation, usually by upregulating the expression of telomerase so as to maintain telomere length, would thus explain why ∼90% of all tumors express high levels of telomeras”
BackgroundSelf-citationXiao, L., Yuan, X., & Sharkis, S. J. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0299 · Cited by 354
Genomic instability and colon cancer
Grady, W. M. (2003) · Cancer and Metastasis Reviews · doi:10.1023/a:1025861527711 · Cited by 354
Natural and pharmacological regulation of telomerase
Mergny, J. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.4.839 · Cited by 355
Pain, B., Clark, M. E., Shen, M., Nakazawa, H., Sakurai, M., Samarut, J., & Etches, R. J. (1996) · Development · doi:10.1242/dev.122.8.2339 · Cited by 352
Tchkonia, T., Lenburg, M. E., Thomou, T., Giorgadze, N., Frampton, G. M., Pirtskhalava, T., Cartwright, A., Cartwright, M., Flanagan, J. N., Karagiannides, I., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00202.2006 · Cited by 365
Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
Kyo, S., Takakura, M., Fujiwara, T., & Inoue, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00878.x · Cited by 347
Forsyth, N. R., Wright, W. E., & Shay, J. W. (2002) · Differentiation · doi:10.1046/j.1432-0436.2002.690412.x · Cited by 345
Self-citationNair, S. K., Heiser, A., Boczkowski, D., Majumdar, A. S., Naoe, M., LEBKOWSKI, J. S., Vieweg, J., & Gilboa, E. (2000) · Nature Medicine · doi:10.1038/79519 · Cited by 348
Reconstitution of human telomerase activity in vitro
Beattie, T. L., Zhou, W., Robinson, M. O., & Harrington, L. A. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70067-3 · Cited by 345
“[24]) were carried out at the Ontario Cancer Institute.”
Regulation of human telomerase in homeostasis and disease
Roake, C. M., & Artandi, S. E. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0234-z · Cited by 356
Telomeric DNA in ALT Cells Is Characterized by Free Telomeric Circles and Heterogeneous t-Loops
Cesare, A. J., & Griffith, J. D. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.22.9948-9957.2004 · Cited by 358
“This occurs most commonly, in approximately 90 to 95% of human cancers and 60 to 70% of immortalized human cell lines, through the upregulation of telomerase ( 19 , 37).”
BackgroundProstate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo
Gu, G., Yuan, J., Wills, M. L., & Kasper, S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4608 · Cited by 347
A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length
Askree, S. H., Yehuda, T., Smolikov, S., Gurevich, R., Hawk, J. D., Coker, C., Krauskopf, A., Kupiec, M., & McEachern, M. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401263101 · Cited by 345
Inhibition of human telomerase activity by peptide nucleic acids
Norton, J. C., Piatyszek, M. A., Wright, W. E., Shay, J. W., & Corey, D. R. (1996) · Nature Biotechnology · doi:10.1038/nbt0596-615 · Cited by 342
Self-citationStrahl, C., & Blackburn, E. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.1.53 · Cited by 335
Ferguson, L. R., Chen, H., Collins, A. R., Connell, M., Damia, G. L. M., Dasgupta, S., Malhotra, M., Meeker, A. K., Amedei, A., Amin, A., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.005 · Cited by 352
“In the majority of human cancers, the telomere specific reverse transcriptase telomerase, which is stringently repressed in normal somatic cells, is activated, thereby restabilizing the telomeres, although cancer telomeres on average seem to remain very short [32,41–45].”
Reed, J. E., Arola‐Arnal, A., Neidle, S., & Vilar, R. (2006) · Journal of the American Chemical Society · doi:10.1021/ja058509n · Cited by 347
Telomerase: A target for cancer therapeutics
Shay, J. W., & Wright, W. E. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00159-9 · Cited by 334
“The almost universal path to overcoming the telomere mitotic clock is the reactivation or upregulation of telomerase (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundSelf-citationAccelerated telomere shortening in ataxia telangiectasia
Metcalfe, J. A., Parkhill, J., Campbell, L. J., Stacey, M. W., Biggs, P., Byrd, P. J., & Taylor, A. M. R. (1996) · Nature Genetics · doi:10.1038/ng0796-350 · Cited by 338
Canela, A., Vera, E., Klatt, P., & Blasco, M. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609367104 · Cited by 347
COMPARISON OF SCREENING METHODS IN THE DETECTION OF BLADDER CANCER
Ramakumar, S., Bhuiyan, J., Besse, J. A., ROBERTS, S. G., Wollan, P. C., Blute, M. L., & O’Kane, D. J. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(01)61899-8 · Cited by 335
Bharadwaj, S., Liu, G., Shi, Y., Wu, R., Yang, B., He, T., Fan, Y., Lu, X., Zhou, X., Liu, H., et al. (2013) · Stem Cells · doi:10.1002/stem.1424 · Cited by 322
Mechanism of Human Telomerase Inhibition by BIBR1532, a Synthetic, Non-nucleosidic Drug Candidate
Pascolo, E., Wenz, C., Lingner, J., Hauel, N. H., Priepke, H. W. M., Kauffmann, I., Garin‐Chesa, P., Rettig, W. J., Damm, K., & Schnapp, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201266200 · Cited by 336
Song, L.-B., Zeng, M., Liao, W., Zhang, L., Mo, H., Liu, W.-L., Shao, J., Wu, Q., Li, M.-Z., Xia, Y.-F., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0094 · Cited by 331
“protocol assay according to the previously published protocol (27).”
MethodAllsopp, R. C., Morin, G. B., DePinho, R., Harley, C. B., & Weissman, I. L. (2003) · Blood · doi:10.1182/blood-2002-07-2334 · Cited by 324
Self-citationStructural Basis of DNA Quadruplex Recognition by an Acridine Drug
Campbell, N. H., Parkinson, G. N., Reszka, A. P., & Neidle, S. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8016973 · Cited by 338
Telomere lengths are characteristic in each human individual
Takubo, K., Izumiyama‐Shimomura, N., Honma, N., Sawabe, M., Arai, T., Kato, M., Oshimura, M., & Nakamura, K. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00218-2 · Cited by 330
Xu, D., Popov, N., Hou, M., Wang, Q., Björkholm, M., Gruber, A., Menkel, A. R., & Arsenian‐Henriksson, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.071043198 · Cited by 324
Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA
Xu, Y. (2011) · Chemical Society Reviews · doi:10.1039/c0cs00134a · Cited by 326
Mechanisms of cancer resistance in long-lived mammals
Seluanov, A., Gladyshev, V. N., Vijg, J., & Gorbunova, V. A. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0004-9 · Cited by 349
Telomeres and telomerase in aging and cancer
Harley, C. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80016-6 · Cited by 322
Self-citationA Pilot Study of the Telomerase Inhibitor Imetelstat for Myelofibrosis
Tefferi, A., Lasho, T. L., Begna, K. H., Patnaik, M. M., Zblewski, D., Finke, C. M., Laborde, R. R., Wassie, E. A., Schimek, L., Hanson, C. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1310523 · Cited by 327
Structural Insights into G-Quadruplexes: Towards New Anticancer Drugs
Yang, D., & Okamoto, K. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.172 · Cited by 327
“Telomerase is activated in 80–85% of human cancer cells [72] and has been suggested to play a key role in maintaining the malignant phenotype by stabilizing telomere length and integrity [73].”
BackgroundMechanisms that Regulate Stem Cell Aging and Life Span
Signer, R. A. J., & Morrison, S. J. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.01.001 · Cited by 320
“Gate-keeping tumor suppressors (such as p16Ink4a, p19Arf, and p53—see Figure 2) negatively regulate cellular proliferation and survival (Kinzler and Vogelstein, 1997).”
Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution
Phan, A. T., Luu, K. N., & Patel, D. J. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl726 · Cited by 326
“Telomerase, an enzyme that can elongate this strand, is not activated in normal human somatic cells, but highly expressed in 80–85% cancer cells and helps to maintain the length of telomeres in these cells (8).”
BackgroundTelomere Length and All-Cause Mortality: A Meta-analysis
Wang, Q., Zhan, Y., Pedersen, N. L., Fang, F., & Hägg, S. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.09.002 · Cited by 333
Constitutive telomerase expression promotes mammary carcinomas in aging mice
Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., Castrillon, D. H., Horner, J. W., Weiler, S. R., Carrasco, R. D., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.112515399 · Cited by 317
Zhang, Z., Yang, X., Zhang, Y., Zeng, B., Wang, S., Zhu, T., Roden, R. B. S., Chen, Y., & Yang, R. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2831 · Cited by 320
Role for the Related Poly(ADP-Ribose) Polymerases Tankyrase 1 and 2 at Human Telomeres
Cook, B. D., Dynek, J. N., Chang, W., Shostak, G., & Smith, S. H. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.1.332-342.2002 · Cited by 319
Involvement of 14‐3‐3 proteins in nuclear localization of telomerase
Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., & Tsuruo, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.11.2652 · Cited by 318
Telomere length homeostasis requires that telomerase levels are limiting
Cristofari, G., & Lingner, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600952 · Cited by 322
What has senescence got to do with cancer?
Dimri, G. P. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.025 · Cited by 323
“More than 90% of tumors contain readily detectable telo merase activity (Kim et al., 1994).”
BackgroundHodes, R. J., Hathcock, K. S., & Weng, N. (2002) · Nature reviews. Immunology · doi:10.1038/nri890 · Cited by 317
“It was proposed initially that telomerase is expressed in germ-line cells — for which the maintenance of telomeres is crucial to fertility — and in transformed cells that are immortalized or have unlimited growth capacity, but not in normal somatic cell”
BackgroundThe Pin2/TRF1-Interacting Protein PinX1 Is a Potent Telomerase Inhibitor
Zhou, X. Z., & Lu, K. P. (2001) · Cell · doi:10.1016/s0092-8674(01)00538-4 · Cited by 311
Understanding TERT Promoter Mutations: A Common Path to Immortality
Bell, R. J. A., Rube, H. T., Xavier‐Magalhães, A., Costa, B. M., Mancini, A., Song, J. S., & Costello, J. (2016) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0003 · Cited by 316
“Telomerase activity is silenced in the majority of normal tissues, causing telomeres to shorten with each successive round of cell division (9, 10).”
Mathon, N. F., & Lloyd, A. C. (2001) · Nature reviews. Cancer · doi:10.1038/35106045 · Cited by 313
“Most human malignant tumours express telomerase; those that don't, stabilize their telomeres by a different mechanism — alternative lengthening of telomeres ( ALT”
BackgroundEpithelial to Mesenchymal Transition in Human Breast Cancer Can Provide a Nonmalignant Stroma
PETERSEN, O. W., Nielsen, H. L., Guðjónsson, Þ., Villadsen, R., Rank, F. E., Niebuhr, E., Bissell, M. J., & Rønnov‐Jessen, L. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63834-5 · Cited by 305
New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin
Chan, S. W.-L., & Blackburn, E. H. (2002) · Oncogene · doi:10.1038/sj.onc.1205082 · Cited by 307
“Cancer cells, with their unchecked proliferation, typically contain active telomerase, which is frequently upregulated to high levels (Kim et al., 1994).”
BackgroundProximal location of mouse prostate epithelial stem cells
Tsujimura, A., Koikawa, Y., Salm, S. N., Takao, T., Coetzee, S., Moscatelli, D., Shapiro, E., Lepor, H., Sun, T., & Wilson, E. L. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200202067 · Cited by 305
“, 1998), which is associated with the germinative compartments of many self-renewing tissues (Kim et al., 1994; Wright et al., 1996).”
BackgroundPersistent Telomere Damage Induces Bypass of Mitosis and Tetraploidy
Davoli, T., Denchi, E. L., & de Lange, T. (2010) · Cell · doi:10.1016/j.cell.2010.01.031 · Cited by 298
“This process eventually limits cellular proliferation through the induction of apoptosis or senescence and is thought to represent a tumor-suppressor mechanism that can be subverted by the activation of telomerase (Kim et al., 1994; Bodnar et al., 1998).”
Gowan, S. M., Harrison, J. R., Patterson, L., Valenti, M. R., Read, M. A., Neidle, S., & Kèlland, L. R. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.5.1154 · Cited by 313
“BRACO19 has been evaluated according to an established cascade as described for the above-mentioned compounds (Kelland, 2001), comprising an initial comparison of cell-free telomerase inhibitory activity in the TRAP assay (Kim et al., 1994) versus acute cytotoxicity against a small panel of human cancer cell lines (Pe…”
Henson, J. D., Hannay, J. A. F., McCarthy, S. W., Royds, J. A., Yeager, T. R., Robinson, R. A., Wharton, S. B., Jellinek, D. A., Arbuckle, S. M., Yoo, J., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.217.11.1 · Cited by 307
Telomere length predicts survival independent of genetic influences
Bakaysa, S. L., Mucci, L. A., Slagboom, P. E., Boomsma, D. I., McClearn, G. E., Johansson, B. E. A., & Pedersen, N. L. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00340.x · Cited by 304
“In contrast, 80% of human cancers show increased telomerase activity ( Kim et al ., 1994 ), resulting in retained telomere length in spite of replication of the tumor cells.”
BackgroundOstenfeld, T., Caldwell, M. A., Prowse, K. R., Linskens, M. H. K., Jauniaux, E. R. M., & Svendsen, C. N. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7427 · Cited by 303
Self-citationBone Marrow Stromal Cells (BMSCs) in Bone Engineering: Limitations and Recent Advances
Derubeis, A. R., & Cancedda, R. (2003) · Annals of Biomedical Engineering · doi:10.1023/b:abme.0000007800.89194.95 · Cited by 301
Does a Sentinel or a Subset of Short Telomeres Determine Replicative Senescence?
Zou, Y., Sfeir, A., Gryaznov, S. M., Shay, J. W., & Wright, W. E. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-03-0207 · Cited by 293
“through the upregulation of telomerase ( Kim et al., 1994; Shay and Bacchetti, 1997) or the”
BackgroundSelf-citationGene perturbation and intervention in probabilistic Boolean networks
Shmulevich, I., Dougherty, E. R., & Zhang, W. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.10.1319 · Cited by 298
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BackgroundTelomerase Regulation, Cell Cycle, and Telomere Stability in Primitive Hematopoietic Cells
Engelhardt, M. M., Kumar, R., Albanell, J., Pettengell, R., Han, W., & Moore, M. A. S. (1997) · Blood · doi:10.1182/blood.v90.1.182 · Cited by 296
Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer.
Takakura, M., Kyo, S., Kanaya, T., Tanaka, M., & Inoue, M. (1998) · PubMed · Cited by 294
Cancer and aging: a model for the cancer promoting effects of the aging stroma
Krtolica, A., & Campisi, J. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00053-5 · Cited by 295
Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation
Fehrmann, F., & Laimins, L. A. (2003) · Oncogene · doi:10.1038/sj.onc.1206554 · Cited by 298
The nature of telomere fusion and a definition of the critical telomere length in human cells
Capper, R., Britt-Compton, B., Tankimanova, M., Rowson, J., Letsolo, B., Man, S., Haughton, M., & Baird, D. M. (2007) · Genes & Development · doi:10.1101/gad.439107 · Cited by 294
“They occur early in tumor development, after which the genome appears to stabilize with advancing malignancy, roughly coincident with the activation of telomerase (Kim et al. 1994; Chadeneau et al. 1995; Meyerson et al. 1997).”
BackgroundReevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action
Cian, A. D., Cristofari, G., Reichenbach, P., Lemos, E. D., Monchaud, D., Teulade‐Fichou, M., Shin‐ya, K., Lacroix, L., Lingner, J., & Mergny, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707365104 · Cited by 302
Holtan, S. G., Creedon, D. J., Haluska, P., & Markovic, S. N. (2009) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)60669-1 · Cited by 315
“For example, increased telomerase activity, typically not observed to a substantial degree in normal somatic cells, is detectable in 85% of human cancers.(55) In fact, the intracellular concentration of telomerase is exponentially related to the proliferative capacity of a cell.”
BackgroundComparison of telomere length measurement methods
Lai, T., Wright, W. E., & Shay, J. W. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0451 · Cited by 301
Self-citationMa, D., Che, C., & Yan, S. (2008) · Journal of the American Chemical Society · doi:10.1021/ja806045x · Cited by 293
Dual Quantification of MicroRNAs and Telomerase in Living Cells
Ma, W., Fu, P., Sun, M., Xu, L., Kuang, H., & Xu, C. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b03617 · Cited by 290
Progress in understanding the molecular pathogenesis of human lung cancer
Sekido, Y., Fong, K. M., & Minna, J. D. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(98)00010-9 · Cited by 289
Canine tumors: a spontaneous animal model of human carcinogenesis
Pinho, S. S., Carvalho, S., Cabral, J., Reis, C. A., & Gärtner, F. (2011) · Translational research · doi:10.1016/j.trsl.2011.11.005 · Cited by 298
Tankyrase-targeted therapeutics: expanding opportunities in the PARP family
Riffell, J. L., Lord, C. J., & Ashworth, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3868 · Cited by 303
Strub, T., Giuliano, S., Ye, T., Bonet, C., Keime, C., Kobi, D., Le Gras, S., Cormont, M., Ballotti, R., Bertolotto, C., et al. (2011) · Oncogene · doi:10.1038/onc.2010.612 · Cited by 269
“Telomerase reverse transcriptase is required for the proper replication of telomeres and is frequently expressed in human tumours, but not in normal somatic cells (Kim et al., 1994; Rudolph et al., 1999; Artandi and DePinho, 2000, 2010).”
BackgroundT Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4 + T Cell Turnover
Wolthers, K. C., Bea, G., Wisman, A., Otto, S. A., de Roda Husman, A.-M., Schaft, N., de Wolf, F., Goudsmit, J., Coutinho, R. A., van der Zee, A. G. J., et al. (1996) · Science · doi:10.1126/science.274.5292.1543 · Cited by 286
Mechanisms of neuroblastoma regression
Brodeur, G. M., & Bagatell, R. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.168 · Cited by 294
Houghtaling, B. R., Cuttonaro, L., Chang, W., & Smith, S. H. (2004) · Current Biology · doi:10.1016/j.cub.2004.08.052 · Cited by 305
Differential regulation of telomerase activity and telomerase RNA during multi-stage tumorigenesis
Blasco, M. A., Rizen, M., Greider, C. W., & Hanahan, D. (1996) · Nature Genetics · doi:10.1038/ng0296-200 · Cited by 287
Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle
Seto, A. G., Zaug, A. J., Sobel, S. G., Wolin, S. L., & Cech, T. R. (1999) · Nature · doi:10.1038/43694 · Cited by 281
Isolation and Characterization of Pluripotent Human Spermatogonial Stem Cell-Derived Cells
Kossack, N. J., Meneses, J. J., Shefi, S., Nguyen, H. N., Chavez, S. L., Nicholas, C. R., Gromoll, J., Turek, P. J., & Pera, R. A. R. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0439 · Cited by 282
“In immortal cells, such as hESCs, germ cells, or cancer cells, the shortening of telomere length is prevented by telomerase [56–58].”
Branche, H. L., Dupuis, S., Ben‐David, Y., Bani, M. R., Wellinger, R. J., & Chabot, B. (1998) · Nature Genetics · doi:10.1038/575 · Cited by 286
“Cell immortalization requires telomere stabilization and has been associated with the activation of telomeras”
BackgroundLataillade, J.-J., Doucet, C., Bey, E., Carsin, H., Huet, C., Clairand, I., Bottollier-Depois, J. F., Chapel, A., Ernou, I., Gourven, M., et al. (2007) · Regenerative Medicine · doi:10.2217/17460751.2.5.785 · Cited by 280
“[13].”
Wick, M., Zubov, D., & Hagen, G. (1999) · Gene · doi:10.1016/s0378-1119(99)00108-0 · Cited by 285
Veldman, T., Horikawa, I., Barrett, J. C., & Schlegel, R. (2001) · Journal of Virology · doi:10.1128/jvi.75.9.4467-4472.2001 · Cited by 286
“Using a modified TRAP assay (17, 35), telomerase activity was detected in HFKs expressing E6 alone or E6 plus E7 but not in HFKs expressing E7 alone.”
BackgroundMethodInfluentialSonoda, Y., Ozawa, T., Hirose, Y., Aldape, K. D., McMahon, M., Berger, M. S., & Pieper, R. O. (2001) · PubMed · Cited by 278
Chiba, K., Lorbeer, F. K., Shain, A. H., McSwiggen, D. T., Schruf, E., Oh, A., Ryu, J., Darzacq, X., Bastian, B. C., & Hockemeyer, D. F. (2017) · Science · doi:10.1126/science.aao0535 · Cited by 283
“Telomere maintenance is essential for cancer cell immortalization (22).”
Structure of a G-quadruplex–Ligand Complex
Haider, S. M., Parkinson, G. N., & Neidle, S. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)01354-2 · Cited by 278
Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)
Poole, J. C., Andrews, L. G., & Tollefsbol, T. O. (2001) · Gene · doi:10.1016/s0378-1119(01)00440-1 · Cited by 280
Molecular Pathogenesis of Osteosarcoma
Kansara, M., & Thomas, D. M. (2007) · DNA and Cell Biology · doi:10.1089/dna.2006.0505 · Cited by 280
Replicative senescence: a critical review
Cristofalo, V. J., Lorenzini, A., Allen, R. G., Torres, C. A., & Tresini, M. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.07.010 · Cited by 285
“The majority of malignant tumors have high telomerase activity and so does the majority of immortal cell lines (Kim et al., 1994; Kyo et al., 1997a,b; Sharpless and DePinho, 2004; Shay and Wright, 2002).”
BackgroundRecent advances in ginseng as cancer therapeutics: a functional and mechanistic overview
Wong, A. S. T., Che, C., & Leung, K. W. (2014) · Natural Product Reports · doi:10.1039/c4np00080c · Cited by 274
Molecular-pathological prognostic factors of gastric cancer: a review
Yasui, W., Oue, N., Aung, P. P., Matsumura, S., Shutoh, M., & Nakayama, H. (2005) · Gastric Cancer · doi:10.1007/s10120-005-0320-0 · Cited by 274
“The maintenance of telomeres by telomerase activation induces cellular immortalization and participates in carcinogenesis [25].”
Subsenescent Telomere Lengths in Fibroblasts Immortalized by Limiting Amounts of Telomerase
Ouellette, M. M., Liao, M., Herbert, B., Johnson, M. D. D., Holt, S. E., Liss, H. S., Shay, J. W., & Wright, W. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10072 · Cited by 272
Self-citationAdriamycin-induced Senescence in Breast Tumor Cells Involves Functional p53 and Telomere Dysfunction
Elmore, L. W., Rehder, C. W., Di, X. M., McChesney, P. A., Jackson‐Cook, C. K., Gewirtz, D. A., & Holt, S. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205477200 · Cited by 275
Telomere lengthening and telomerase activation during human B cell differentiation
Weng, N., Granger, L., & Hodes, R. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10827 · Cited by 272
Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization
Lim, C. J., & Cech, T. R. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00328-y · Cited by 273
In vivo Inhibition of Lung Cancer by GRN163L: A Novel Human Telomerase Inhibitor
Dikmen, Z. G., Gellert, G. C., Jackson, S., Gryaznov, S., Tressler, R., Dogan, P., Wright, W. E., & Shay, J. W. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1215 · Cited by 271
“Telomerase is active in 85% to 90% of all human tumors but not in normal somatic cells with the exception of germ line and select progenitor cell populations (10, 11).”
BackgroundSelf-citationHerbert, B., Gellert, G. C., Hochreiter, A. E., Pongracz, K., Wright, W. E., Zielińska, D., Chin, A. C., Harley, C. B., Shay, J. W., & Gryaznov, S. M. (2005) · Oncogene · doi:10.1038/sj.onc.1208760 · Cited by 269
“The TRAP assay was performed with the TRAP-eze Telomerase Detection kit (Serologicals/Invitrogen) and established protocols (Kim et al., 1994; Piatyszek et al., 1995; Wright et al., 1995).”
MethodSelf-citationNonradioactive detection of telomerase activity using the telomeric repeat amplification protocol
Herbert, B., Hochreiter, A. E., Wright, W. E., & Shay, J. W. (2006) · Nature Protocols · doi:10.1038/nprot.2006.239 · Cited by 269
“TRAP was developed as a PCR-based method to assess the level of telomerase activity in a given sampl”
MethodSelf-citation
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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