Cited by 1,279Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsDNA and Nucleic Acid Chemistry

Telomere elongation in immortal human cells without detectable telomerase activity

Open access
Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., Reddel, R. R.·1995·The EMBO Journal

Abstract

Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell lines, 20 had telomerase activity as expected, but 15 had no detectable telomerase. The 15 telomerase-negative immortalized cell lines all had very long and heterogeneous telomeres of up to 50 kb. Hybrids between telomerase-negative and telomerase-positive cells senesced. Two senescent hybrids demonstrated telomerase activity, indicating that activation of telomerase is not sufficient for immortalization. Some hybrid clones subsequently recommenced proliferation and became immortalized either with or without telomerase activity. Those without telomerase activity also had very long and heterogeneous telomeres. Taken together, these data suggest that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.

Integrity signals

Registry

Crossref · 10.1002/j.1460-2075.1995.tb00098.x

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • 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”
  • In telomerase-negative normal human lung fibroblasts and ALT-phenotype SAOS-2 osteosarcoma cells, inhibitor treatment did not affect telomere length, growth kinetics or morphology over 8 weeks.

    “Our results showed that inhibitor treatment had no effect on telomere length, growth kinetics and morphology for the entire time of treatment (8 weeks) in either cell line.”

    From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Bryan et al., 1995

  • An ALT mechanism has been described for virus-transformed human cells and a small proportion of established human cancer cell lines that lack telomerase activity.

    “A similar ALT mechanism has been described for virustransformed human cells and a small proportion of established human cancer cell lines that lack telomerase activity (Bryan et al., 1995).”

    From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Bryan et al., 1995

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., & Reddel, R. R.
Affiliations
Children's Medical Research Institute (AU)
Venue
The EMBO Journal
Published
1995-09-01
Volume
14
Issue
17
Pages
4240-4248
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W1600373583
Cited by
1,279
References
45
Citations by year
2026: 12 · 2025: 16 · 2024: 26 · 2023: 30 · 2022: 59 · 2021: 35 · 2020: 36 · 2019: 43 · 2018: 27 · 2017: 35 · 2016: 36 · 2015: 33 · 2014: 33 · 2013: 45 · 2012: 43
FWCI
34.02
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of Sydney
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
telomere elongation, telomerase, cell immortalization, telomere length, cellular senescence, human fibroblasts
MeSH terms
Base Sequence, Cell Line, Cell Line, Transformed, Cell Transformation, Viral, Clone Cells, Enzyme Activation, Humans, Hybrid Cells, Repetitive Sequences, Nucleic Acid, Simian virus 40, Polymerase Chain Reaction, Telomere, Cellular Senescence, Telomerase

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