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]
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“Telomeres are primarily controlled by a highly specialized DNA polymerase, termed telomerase, which is activated in most human cancers and immortal cell lines (16, 17); the mechanisms of activation and regulation of telomerase, however, have yet to be established.”
BackgroundVaccination of Cancer Patients Against Telomerase Induces Functional Antitumor CD8+ T Lymphocytes
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“Because 85% of all human cancers express telomerase activity (5), there is potential to extend strategies of hTERT-specific immunotherapy to the majority of patients with common cancers.”
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“Activation of telomerase is the critical step for the immortalization of more than 90% of all human tumors ( Greider and Blackburn, 1985 ; Counter, 1992 ; Kim et al., 1994 ).”
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“A recently developed PCR-based assay (25, 51) was used to measure telomerase activity in culture A and culture C cells.”
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“Due to the absence of telomerase (Kim et al., 1994), telomeres shorten with cell”
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“Telomerase is generally only expressed in stem cells in adult humans, but becomes reactivated in many cancer”
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“The current interest in G-rich telomeric DNA folded into quadruplex structures stems from its attractiveness as an anti-cancer target, linked to the ribonucleoprotein telomerase, an enzyme that maintains chromosomal integrity and is up-regulated in >85% of various human cancers types (13).”
BackgroundStable Association of hsp90 and p23, but Not hsp70, with Active Human Telomerase
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“Telomerase is activated in 90% of tumors and this activation is thought to confer immortal growth properties on the tumor cells (Kim et al., 1994; Shay and Bacchetti, 1997).”
BackgroundAgeing and telomeres: a study into organ- and gender-specific telomere shortening
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“Consistent with this observation, some investigators have reported that most somatic cells do not express telomerase (36, 37 ).”
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“Telomerase is either absent or present at low levels in most normal human somatic cells (3, 24).”
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“Telomerase expression is frequently high in cancer and immortalized cells but generally low in most normal and senescent cells Kim et al. 1994).”
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“In contrast, there are activity assays for telomerase (the most widely used being the TRAP assay [15]), which was originally detected by its enzymatic activity [16].”
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“…of tumor cells and germ line cells overcome this proliferative limit by the action of telomerase, a ribonucleoprotein with reverse transcriptase activity that adds telomeric DNA repeats to the 30 overhang of telomeres (Collins and Mitchell, 2002; Greider and Blackburn, 1985; Kim et al., 1994).”
BackgroundSelf-citationA novel telomerase template antagonist (GRN163) as a potential anticancer agent.
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“Telomerase activity is constitutively expressed in germline cells and in the majority of malignant tumor cells and is repressed in most human normal somatic cells (4, 5).”
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“In approximately 85% of human cancers, however, telomerase is reactivated and acts to maintain telomere length, usually at relatively short lengths in the region of 3 to 8 kb (Kim et al., 1994; Holt and Shay, 1999; Chu et al., 2000).”
The hTERTα Splice Variant is a Dominant Negative Inhibitor of Telomerase Activity
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“The most common means by which such cells stabilize their telomeres is by expressing telomerase, speci®cally the catalytic component, TERT (Kim et al., 1994; Chiu and Harley, 1997; Shay and Wright, 2001).”
BackgroundInfluentialPaternal age is positively linked to telomere length of children
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“Indeed, telomerase is activated in most human tumors ( Kim et al ., 1994 ).”
BackgroundThe catalytic subunit of yeast telomerase
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“001 until the telomeres reach a critical length, at which point the cells enter senescence [11].”
BackgroundCell cycle-dependent modulation of telomerase activity in tumor cells.
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“Human ES cell lines express high levels of telomerase activity that seems to be correlated with immortality[13, 26].”
BackgroundTelomere dysfunction and the initiation of genome instability
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“This occurs by the action of the reverse transcriptase telomerase, which is not normally expressed in somatic cells and which catalyses the synthesis of telomeric DNA repeats to balance those lost during replicatio”
BackgroundOlivero, O. A., Yuspa, S. H., Poirier, M. C., Anderson, L. M., Jones, A. B., Wang, C., Diwan, B. A., Haines, D. C., Logsdon, D. M., Harbaugh, S. W., et al. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.21.1602 · Cited by 223
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“Such an effect has profound implications in cancer cells, the majority of which have over-expressed levels of telomeras”
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“This assay is derived from the classical TRAP assay initially proposed in 1994 (28).”
MethodRNA G-quadruplexes (rG4s): genomics and biological functions
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“Telomerase is responsible for telomere maintenance, and was found to be upregulated in most cancer cells (168).”
BackgroundBiology of premature ageing in survivors of cancer
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“Since most immortalized cells and tumors have telomerase activity (16) and expression of the catalytic unit of telomerase (hTERT) prolongs the life span of primary fibroblasts (3, 47, 48), we determined whether MOF levels change in cells with a prolonged life span.”
BackgroundLgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes
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“Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes”
BackgroundTelomerase Mechanism of Telomere Synthesis
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“More than a decade later telomerase was detected in cells other than ciliates, first in the immortalized human cancer cell line HeLa (21) and eventually in a wide range of human cancers (22).”
BackgroundExpression of mouse telomerase catalytic subunit in embryos and adult tissues
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Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells
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Telomere Maintenance Requires the RAD51D Recombination/Repair Protein
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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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