hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

Valls-Bautista,Cristina; Bougel,Stéphanie; Piñol‑Felis,Carme; Viñas-Salas,Joan; Benhattar,Jean

doi:10.3892/ol.2011.386

hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells

Authors:
- Cristina Valls-Bautista
- Stéphanie Bougel
- Carme Piñol‑Felis
- Joan Viñas-Salas
- Jean Benhattar
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Affiliations: Department of Medicine, Medical School, Lleida University, Lleida, Spain, Institute of Pathology, CHUV and University of Lausanne, 1011 Lausanne, Switzerland
Published online on: August 18, 2011 https://doi.org/10.3892/ol.2011.386
Pages: 1257-1260

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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 telome-rase 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 methy-lation 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, methy-lation is not sufficient for hTERT activation, particularly in normal colorectal cells.

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