Telomere elongation in immortal human cells without detectable telomerase activity

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...

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Published inThe EMBO journal Vol. 14; no. 17; pp. 4240 - 4248
Main Authors Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., Reddel, R. R.
Format Journal Article
LanguageEnglish
Published England 01.09.1995
Subjects
Base Sequence
Cell Line
Cell Line, Transformed
Cell Transformation, Viral
Cellular Senescence
Clone Cells
Enzyme Activation
Humans
Hybrid Cells
Polymerase Chain Reaction
Repetitive Sequences, Nucleic Acid
Simian virus 40
Telomerase - analysis
Telomerase - deficiency
Telomerase - metabolism
Telomere - physiology
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Summary: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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:0261-4189
1460-2075
DOI:10.1002/j.1460-2075.1995.tb00098.x