Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals

Several reports have shown that the ectopic expression of the human telomerase catalytic subunit gene (h TERT) leads to an indefinite extension of the life span of human fibroblasts cultured in vitro without the appearance of cancer-associated changes. We infected two fibroblast strains derived from...

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Published in:Biochemical and biophysical research communications 2003-09, Vol.308 (4), p.914-921
Main Authors: Mondello, Chiara, Chiesa, Massimo, Rebuzzini, Paola, Zongaro, Samantha, Verri, Annalisa, Colombo, Tina, Giulotto, Elena, D’Incalci, Maurizio, Franceschi, Claudio, Nuzzo, Fiorella
Format: Article
Language:English
Subjects:
Agar - metabolism
Aged
Aged, 80 and over
Aging
Anchorage-independent growth
Cell Adhesion
Cell Division
Cell Transformation, Neoplastic
Cellular immortalization
Cellular Senescence
Cellular transformation
Centenarians
Centromere - ultrastructure
Chromosome Aberrations
DNA - metabolism
DNA-Binding Proteins
Female
Fibroblasts - metabolism
Humans
Karyotype instability
Karyotyping
Retroviridae - genetics
Telomerase
Telomerase - genetics
Telomerase - metabolism
Telomere - ultrastructure
Telomeres
Time Factors
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Summary:Several reports have shown that the ectopic expression of the human telomerase catalytic subunit gene (h TERT) leads to an indefinite extension of the life span of human fibroblasts cultured in vitro without the appearance of cancer-associated changes. We infected two fibroblast strains derived from centenarian individuals with an h TERT containing retrovirus and isolated transduced massive populations (cen2tel and cen3tel). In both populations, h TERT expression reconstituted telomerase activity and extended the life span. In cen2tel, a net telomere lengthening was observed while, in cen3tel, telomeres stabilized at a length lower than that detected in senescent parental cells. Interestingly, both cen2tel and cen3tel cells developed chromosome anomalies, numerical first and structural thereafter. Moreover, cen3tel cells acquired the ability to grow in the absence of solid support, a typical feature of transformed cells. The results we present here highlight an unexpected possible outcome of cellular immortalization driven by telomerase reactivation, and indicate that, in some cases, an artificial extension of cellular replicative capacity can increase the probability of occurrence of genomic alterations, which can lead to cellular transformation.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)01484-0