Telomerase Extends the Lifespan of Virus-Transformed Human Cells without Net Telomere Lengthening

Human fibroblasts whose lifespan in culture has been extended by expression of a viral oncogene eventually undergo a growth crisis marked by failure to proliferate. It has been proposed that telomere shortening in these cells is the property that limits their proliferation. Here we report that ectop...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-03, Vol.96 (7), p.3723-3728
Main Authors: Zhu, Jiyue, Wang, He, Bishop, J. Michael, Blackburn, Elizabeth H.
Format: Article
Language:English
Subjects:
Antigens, Viral, Tumor - genetics
Biological Sciences
Cell Cycle
Cell Division
Cell growth
Cell Line
Cell lines
Cell Transformation, Viral
Cells
Cellular senescence
Chromosomes
DNA-Binding Proteins
Fibroblasts
HEK293 cells
Humans
Karyotyping
Metaphase
Microbiology
Proteins
Recombinant Proteins - metabolism
RNA
Simian virus 40 - genetics
Telomerase - genetics
Telomerase - metabolism
Telomere - physiology
Telomeres
Transfection
Viruses
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Summary:Human fibroblasts whose lifespan in culture has been extended by expression of a viral oncogene eventually undergo a growth crisis marked by failure to proliferate. It has been proposed that telomere shortening in these cells is the property that limits their proliferation. Here we report that ectopic expression of the wild-type reverse transcriptase protein (hTERT) of human telomerase averts crisis, at the same time reducing the frequency of dicentric and abnormal chromosomes. Surprisingly, as the resulting immortalized cells containing active telomerase continue to proliferate, their telomeres continue to shorten to mean lengths below those in control cells that enter crisis. These results provide evidence for a protective function of human telomerase that allows cell proliferation without requiring net lengthening of telomeres.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.7.3723