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Telomere dysfunction and telomerase activation in cancer - a pathological paradox?

Calcagnile, O. and Gisselsson Nord, David LU (2007) In Cytogenetic and Genome Research 118(2-4). p.270-276
Abstract
Telomerase is expressed in more than 90% of human cancers. Telomere maintenance by this enzyme is believed to safeguard genomic integrity in neoplastic cells. Nevertheless, many telomerase-expressing tumours exhibit chromosomal instability triggered by short, dysfunctional telomeres, implying that active telomerase is not sufficient for preserving a functional telosomic nucleoprotein complex in cancer cells. We here examine three possible solutions to this ostensible paradox. First, prior to telomerase activation, telomere erosion may have evolved to a level where telomeric repeat sequences are too short to provide a functional substrate for telomerase enzyme activity. Second, mechanisms other than the continuous telomere erosion... (More)
Telomerase is expressed in more than 90% of human cancers. Telomere maintenance by this enzyme is believed to safeguard genomic integrity in neoplastic cells. Nevertheless, many telomerase-expressing tumours exhibit chromosomal instability triggered by short, dysfunctional telomeres, implying that active telomerase is not sufficient for preserving a functional telosomic nucleoprotein complex in cancer cells. We here examine three possible solutions to this ostensible paradox. First, prior to telomerase activation, telomere erosion may have evolved to a level where telomeric repeat sequences are too short to provide a functional substrate for telomerase enzyme activity. Second, mechanisms other than the continuous telomere erosion counteracted by telomerase may contribute to rapid shortening of telomere repeats. Third, dysfunction of telomere-regulating proteins may result in direct telomere uncapping. Moreover, telomerase may contribute to tumour development also through mechanisms unrelated to telomere length maintenance. Taken together, the available data on the role of telomerase in cancer strongly support that inhibition of this enzyme is a feasible strategy for cancer therapy. Copyright (C) 2007 S. Karger AG, Basel. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cytogenetic and Genome Research
volume
118
issue
2-4
pages
270 - 276
publisher
Karger
external identifiers
  • wos:000251551300022
  • scopus:36248966581
ISSN
1424-859X
DOI
10.1159/000108310
language
English
LU publication?
yes
id
646f9f62-b01e-4253-801a-e8c50a80f4e6 (old id 966140)
date added to LUP
2008-01-29 13:50:56
date last changed
2017-01-01 04:30:36
@article{646f9f62-b01e-4253-801a-e8c50a80f4e6,
  abstract     = {Telomerase is expressed in more than 90% of human cancers. Telomere maintenance by this enzyme is believed to safeguard genomic integrity in neoplastic cells. Nevertheless, many telomerase-expressing tumours exhibit chromosomal instability triggered by short, dysfunctional telomeres, implying that active telomerase is not sufficient for preserving a functional telosomic nucleoprotein complex in cancer cells. We here examine three possible solutions to this ostensible paradox. First, prior to telomerase activation, telomere erosion may have evolved to a level where telomeric repeat sequences are too short to provide a functional substrate for telomerase enzyme activity. Second, mechanisms other than the continuous telomere erosion counteracted by telomerase may contribute to rapid shortening of telomere repeats. Third, dysfunction of telomere-regulating proteins may result in direct telomere uncapping. Moreover, telomerase may contribute to tumour development also through mechanisms unrelated to telomere length maintenance. Taken together, the available data on the role of telomerase in cancer strongly support that inhibition of this enzyme is a feasible strategy for cancer therapy. Copyright (C) 2007 S. Karger AG, Basel.},
  author       = {Calcagnile, O. and Gisselsson Nord, David},
  issn         = {1424-859X},
  language     = {eng},
  number       = {2-4},
  pages        = {270--276},
  publisher    = {Karger},
  series       = {Cytogenetic and Genome Research},
  title        = {Telomere dysfunction and telomerase activation in cancer - a pathological paradox?},
  url          = {http://dx.doi.org/10.1159/000108310},
  volume       = {118},
  year         = {2007},
}