TY - JOUR
T1 - Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals
AU - Mondello, Chiara
AU - Chiesa, Massimo
AU - Rebuzzini, Paola
AU - Zongaro, Samantha
AU - Verri, Annalisa
AU - Colombo, Tina
AU - Giulotto, Elena
AU - D'Incalci, Maurizio
AU - Franceschi, Claudio
AU - Nuzzo, Fiorella
PY - 2003/9/5
Y1 - 2003/9/5
N2 - 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.
AB - 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.
KW - Anchorage-independent growth
KW - Cellular immortalization
KW - Cellular transformation
KW - Centenarians
KW - Karyotype instability
KW - Telomerase
KW - Telomeres
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UR - http://www.scopus.com/inward/citedby.url?scp=0041659132&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(03)01484-0
DO - 10.1016/S0006-291X(03)01484-0
M3 - Article
C2 - 12927806
AN - SCOPUS:0041659132
VL - 308
SP - 914
EP - 921
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -