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 (hTERT) 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 hTERT containing retrovirus and isolated transduced massive populations (cen2tel and cen3tel). In both populations, hTERT 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.
Mondello
Chiara
C
Istituto di Genetica Molecolare, Via Abbiategrasso 207, Pavia 27100, Italy. mondello@igm.cnr.it
Chiesa
Massimo
M
Rebuzzini
Paola
P
Zongaro
Samantha
S
Verri
Annalisa
A
Colombo
Tina
T
Giulotto
Elena
E
D'Incalci
Maurizio
M
Franceschi
Claudio
C
Nuzzo
Fiorella
F
D000362:Agar / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D002503:Centromere / Q000648:ultrastructure; D002869:Chromosome Aberrations; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007621:Karyotyping; D012190:Retroviridae / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure; D013997:Time Factors
D004268:DNA-Binding Proteins; D000362:Agar; D004247:DNA; D019098:Telomerase