hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells
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Date
2011
Authors
Valls i Bautista, Cristina
Bougel, Stéphanie
Piñol Felis, Carme
Viñas Salas, Joan
Benhattar, Jean
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Abstract
Colorectal cancers exhibit a high telomerase
activity, usually correlated with the hypermethylation of the
promoter of its hTERT catalytic subunit. Although telomerase
is not expressed in normal tissue, certain proliferative
somatic cells such as intestinal crypt cells have demonstrated
telomerase activity. The aim of this study was to determine
whether a correlation exists between telomerase activity,
levels of hTERT methylation and telomere length in tumoral
and normal colorectal tissues. Tumor, transitional and normal
tissues were obtained from 11 patients with a colorectal
cancer. After bisulfite modification of genomic DNA, hTERT
promoter methylation was analyzed by methylation-sensitive
single-strand conformation analysis (MS-SSCA). Telomerase
activity and telomere length were measured by a fluorescent‑
telomeric repeat amplification protocol assay and by Southern
blotting, respectively. A significant increase of hTERT methylation
and telomerase activity, and a reduction of the mean
telomere length were observed in the tumor tissues compared
to the transitional and normal mucosa. In the transitional and
normal mucosa, telomerase activity was significantly lower
than that in tumor tissues, even with high levels of hTERT
methylation. Nevertheless, hTERT promoter methylation was
not linearly correlated to telomerase activity. These data indicate
that hTERT promoter methylation is a necessary event for
hTERT expression, as is telomerase activity. However, methylation
is not sufficient for hTERT activation, particularly in
normal colorectal cells.
Citation
Journal or Serie
Oncology letters, 2011, vol. 2, núm. 6, p.1257-1260