Original Article

Telomere dynamics and genome stability in the human pancreatic tumor cell line MIAPaCa-2
N. krobot Vidaek^a, A. Çukuši^a, M. Ferenac Kiš^a, M. Ivankovi^a, I. Jevtov^a, S. Mrsi^b, I. Rubelj<sup>a

a</sup>Department of Molecular Biology, Ruer Boškovi Institute, and
^bZagreb Clinical Hospital Center, Clinical Institute of Laboratory Diagnosis, Zagreb University School of Medicine, Zagreb (Croatia)

Address of Corresponding Author

Cytogenet Genome Res 2007;119:60-67 (DOI: 10.1159/000109620)

  Abstract.

Telomeres are specialized structures found at the ends of eukaryotic chromosomes serving as guardians of genome stability. In normal cells telomeres shorten with each cell division, but immortal cells undergoing multiple divisions constantly have to maintain telomere lengths above a critical level. This is accomplished either through expression of telomerase or the alternative recombination pathway (ALT). In the present study, we analyzed telomere dynamics of the telomerase positive human pancreatic tumor cell line MIAPaCa-2. The cells demonstrated genomic instability with a high frequency of chromosomal aberrations resulting in differences between individual karyotypes within the same cell population. The telomeres were short when compared with normal human fibroblasts, and about 39% of the chromosome ends did not have detectable telomere repeats as demonstrated by PNA-FISH. In many cases telomere signals were missing even when sister chromatids were strongly labeled. In addition, we used an internal PNA probe specific for the X chromosome, present in a single copy in these cells, in order to follow telomere dynamics on individual chromatids. High heterogeneity in telomere signals among individual X chromosomes as well as between their sister chromatids suggested sudden and stochastic loss or gain of telomere repeats. Such constant genomic instability often results in apoptosis and death of a fraction of cells present in the culture at all times. We discuss possible molecular mechanisms that may explain this observed telomere heterogeneity and possible adaptive repair mechanisms by which these cells maintain their chromosomes in order to survive such extreme and permanent genomic instability.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Request reprints from Ivica Rubelj
Department of Molecular Biology, Ruer Boškovi Institute
Bijenika 54, 10.000 Zagreb (Croatia)
telephone: +385 1 4561 093; fax: +385 1 4561 177
e-mail: rubelj@irb.hr

  Article Information

This work was supported by Croatian Ministry of Science, Education and Sports grant 098-0982913-2768.

Manuscript received: 12 March 2007
Accepted in revised form for publication by A. Geurts van Kessel,: 23 May 2007.
Published online: December 14, 2007
Number of Print Pages : 8
Number of Figures : 7, Number of Tables : 0, Number of References : 51