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Department of
Pathology, University of Antwerp, Universiteitsplein 1, B-2610
Wilrijk/Antwerp, Belgium
Correspondence to: Dr E Van Marck.
Received 20 May 1998; Returned to authors 25 June 1998; Revised version received 24 July 1998; Accepted for publication 27 July 1998
BACKGROUND
Gradual telomere erosion
eventually limits the replicative life span of somatic cells and is
regarded as an ultimate tumour suppressor mechanism, eliminating cells
that have accumulated genetic alterations. Telomerase, which has been
found in over 85% of human cancers, elongates telomeres and may be
required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The
disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in
pleural malignant mesothelioma, which may be the target for future
anti-telomerase drugs.
METHODS
Telomerase activity was
semi-quantitatively measured in extracts from 22 primary pleural
mesotheliomas, two benign solitary fibrous tumours of the pleura, four
mesothelioma cell lines, and six short term mesothelial cell cultures
from normal pleura using a non-isotopic dilution assay of the telomeric
repeat amplification protocol.
RESULTS
Twenty of the 22 primary
mesotheliomas (91%) and all tumour derived mesothelioma cell lines
were telomerase positive. Different levels of enzyme activity were
observed in the tumours of different histological subtypes. Telomerase
activity could not be detected in the six normal mesothelial cell
cultures or in the two mesotheliomas. Both benign solitary fibrous
tumours showed strong telomerase activity.
CONCLUSIONS
Telomerase activity is found in
a high proportion of mesotheliomas and anti-telomerase drugs might
therefore be useful clinically. The results are consistent with the
hypothesis that telomerase activity may be a feature of
carcinogenesis in mesotheliomas and possibly in many other cancers.
This article has been cited by other articles:
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R. Villa, M. G. Daidone, R. Motta, L. Venturini, C. De Marco, A. Vannelli, S. Kusamura, D. Baratti, M. Deraco, A. Costa, et al. Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma Clin. Cancer Res., July 1, 2008; 14(13): 4134 - 4140. [Abstract] [Full Text] [PDF] |
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