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

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Telomere dysfunction and telomerase activation in cancer - a pathological paradox? / Calcagnile, O.; Gisselsson Nord, David.

In: Cytogenetic and Genome Research, Vol. 118, No. 2-4, 2007, p. 270-276.

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T1 - Telomere dysfunction and telomerase activation in cancer - a pathological paradox?

AU - Calcagnile, O.

AU - Gisselsson Nord, David

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1159/000108310

DO - 10.1159/000108310

M3 - Article

VL - 118

SP - 270

EP - 276

JO - Cytogenetic and Genome Research

JF - Cytogenetic and Genome Research

SN - 1424-859X

IS - 2-4

ER -