Super-telomeres in transformed human fibroblasts (Articolo in rivista)

  • Super-telomeres in transformed human fibroblasts (Articolo in rivista) (literal)
  • 2013-01-01T00:00:00+01:00 (literal)
  • 10.1016/j.bbamcr.2013.03.030 (literal)
Alternative label
  • Chiodi I, Belgiovine C, Zongaro S, Ricotti R, Horard B, Lossani A, Focher F, Gilson E, Giulotto E, Mondello C. (2013)
    Super-telomeres in transformed human fibroblasts
    in Biochimica et biophysica acta. Molecular cell research
  • Chiodi I, Belgiovine C, Zongaro S, Ricotti R, Horard B, Lossani A, Focher F, Gilson E, Giulotto E, Mondello C. (literal)
Pagina inizio
  • 1893 (literal)
  • 1883 (literal)
  • 1885 (literal)
  • PubMe (literal)
  • Ilaria Chiodi, Cristina Belgiovine, Samantha Zongaro, Roberta Ricotti,Andrea Lossani, Federico Focher, Chiara Mondello: Istituto di Genetica Molecolare, CNR, Pavia; Beatrice Horard: Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, Lyon, France; Eric Gilson: Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice; Elena Giulotto: Dipartimento di Biologia e Biotecnologie \"Lazzaro Spallanzani\", Università di Pavia, Pavia. (literal)
  • Super-telomeres in transformed human fibroblasts (literal)
  • Telomere length maintenance is critical for organisms' long-term survival and cancer cell proliferation. Telomeres are kept within species-specific length ranges by the interplay between telomerase activity and telomeric chromatin organization. In this paper, we exploited telomerase immortalized human fibroblasts (cen3tel) that gradually underwent neoplastic transformation during culture propagation to study telomere composition and length regulation during the transformation process. Just after telomerase catalytic subunit (hTERT) expression, cen3tel telomeres shortened despite the presence of telomerase activity. At a later stage and concomitantly with transformation, cells started elongating telomeres, which reached a mean length greater than 100 kb in about 900 population doublings. Super-telomeres were stable and compatible with cell growth and tumorigenesis. Telomere extension was associated with increasing levels of telomerase activity that were linked to deregulation of endogenous telomerase RNA (hTERC) and exogenous telomerase reverse transcriptase (hTERT) expression. Notably, the increase in hTERC levels paralleled the increase in telomerase activity, suggesting that this subunit plays a role in regulating enzyme activity. Telomeres ranging in length between 10 and more than 100 kb were maintained in an extendible state although TRF1 and TRF2 binding increased with telomere length. Super-telomeres neither influenced subtelomeric region global methylation nor the expression of the subtelomeric gene FRG1, attesting the lack of a clear-cut relationship between telomere length, subtelomeric DNA methylation and expression in human cells. The cellular levels of the telomeric proteins hTERT, TRF1, TRF2 and Hsp90 raised with transformation and were independent of telomere length, pointing to a role of these proteins in tumorigenesis. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:

Autore CNR di
Insieme di parole chiave di