hTERT methylation is necessary but not sufficient for telomerase activity in colorectal cells
Valls i Bautista, Cristina
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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.
Is part ofOncology letters, 2011, vol. 2, núm. 6, p.1257-1260
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Valls i Bautista, Cristina; Piñol Felis, Carme; Reñé Espinet, Josep Maria; Buenestado Garcia, Juan; Viñas Salas, Joan (Sociedad Española de Patología DigestivaArán Ediciones, 2012)Background: colorectal cancer is the third cancer cause of death in Spain. It is important to investigate new tumoral markers for early diagnosis, disease monitoring and prevention strategies. Telomeres protect the ...
Valls i Bautista, Cristina; Piñol Felis, Carme; Reñé Espinet, Josep Maria; Buenestado Garcia, Juan; Viñas Salas, Joan (Wiley, 2011)Aim The aim of this study was to determine whether telomere length is an independent prognostic factor for the prevention and survival of colorectal cancer. Method Terminal restriction fragment (TRF) length was determined ...
Valls i Bautista, Cristina; Piñol Felis, Carme; Reñé Espinet, Josep Maria; Buenestado Garcia, Juan; Viñas Salas, Joan (Sociedad Española de Patología DigestivaArán Ediciones, 2009)Objective: the role of telomerase activity and telomere length in the adenoma-carcinoma sequence of colon carcinogenesis has not been well established. The objective of this study was to determine telomerase activity and ...