Abstract
The characteristics of B-lymphoblastoid cell strains transformed by Epstein – Barr virus (EBV) from normal individuals and Werner's syndrome (WRN) patients were compared. We continuously passaged cell strains from 28 WRN patients and 20 normal individuals for about 2 years corresponding to over 160 population doubling levels (PDLs). First, the WRN mutation significantly suppressed the immortalization: all the 28 cell strains from WRN patients, as well as 15 out of 20 cell strains from normal individuals, died out before 160 PDLs mostly without developing a significant telomerase activity. The remaining five cell strains from normal individuals became moderately/strongly telomerase-positive and, three of them were apparently immortalized with an infinitively proliferating activity. Second, the monitoring of the telomere length of both normal and WRN cell strains during the culture period suggests that the WRN gene mutation causes abnormal dynamics of the telomere: (1) a significant proportion of WRN cell strains showed drastic shortening or lengthening of telomere lengths during cell passages compared with normal cell strains, and (2) WRN cell strains terminated their life-span at a wide range of telomere length (between 3.5 and 18.5 Kbp), whereas normal cell strains terminated within a narrow telomere length range (between 5.5 and 9 Kbp). The chromosomal aberration characteristic of WRN cells, including translocation was confirmed in our experiment. We discussed the correlation between the chromosomal instability, abnormal telomere dynamics and inability of immortalization of the WRN B-lymphobloastoid cell strains.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tahara, H., Tokutake, Y., Maeda, S. et al. Abnormal telomere dynamics of B-lymphoblastoid cell strains from Werner's syndrome patients transformed by Epstein – Barr virus. Oncogene 15, 1911–1920 (1997). https://doi.org/10.1038/sj.onc.1201377
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201377
Keywords
This article is cited by
-
Stochastic Simulations of Normal Aging and Werner’s Syndrome
Bulletin of Mathematical Biology (2014)
-
On BLM helicase in recombination-mediated telomere maintenance
Molecular Biology Reports (2013)
-
Chromosomal rearrangements after ex vivo Epstein–Barr virus (EBV) infection of human B cells
Oncogene (2010)
-
From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing
Cellular and Molecular Life Sciences (2007)
-
Length-dependent degradation of single-stranded 3' ends by the Werner syndrome protein (WRN): implications for spatial orientation and coordinated 3' to 5' movement of its ATPase/helicase and exonuclease domains
BMC Molecular Biology (2006)