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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Most human cancers (~90%) escape telomere crisis by activating telomerase.
“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]
Telomere function may be required for immortalization, supported by frequent activation of telomerase or ALT in human cancers.
“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
Telomerase is active in roughly 90% of human cancers regardless of tumor type, whereas most normal tissues have inactive telomerase.
“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 <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [1]
Most human cancers have increased telomerase activity, which probably helps them maintain immortality.
“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]
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 ALT.
“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]
Keeping telomeres intact is necessary for malignant cells to keep dividing.
“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
Most human cancers and germline cells have telomerase activity, whereas normal human somatic tissues generally do not.
“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 cancer cells, telomerase reactivation is thought to stabilize telomere length, offset erosion, and give malignant cells unlimited proliferative capacity.
“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
Telomerase activity occurs in immortalized cell lines and in 80-90% of human cancer specimens across many cancer types.
“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
Telomerase activity has been found in almost all human tumors but not in adjacent normal cells.
“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]
Most human cancers activate telomerase at some point during tumorigenesis, while telomerase activity is largely absent in most normal tissues.
“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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- 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
- Health Sciences › Medicine › Physiology › 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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