The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation

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Serval ID
serval:BIB_AD732F095C7B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The human telomerase RNA gene (hTERC) is regulated during carcinogenesis but is not dependent on DNA methylation
Journal
Carcinogenesis
Author(s)
Guilleret  I., Yan  P., Guillou  L., Braunschweig  R., Coindre  J. M., Benhattar  J.
ISSN
0143-3334 (Print)
Publication state
Published
Issued date
2002
Volume
23
Number
12
Pages
2025-2030
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative soft tissue sarcomas (STS), half did not express hTERC at all, or only weakly, whereas a wide range of expression was observed in the other half. As methylation might be involved in hTERC silencing, we examined the methylation pattern in all samples by direct sequencing and methylation-specific single stand conformation analysis after bisulfite modification. hTERC methylation was never observed, neither in normal nor in tumor tissues. Furthermore, there was no correlation between hTERC expression and proliferation, telomere length or hTERT expression in telomerase-negative STS. In contrast, three of eight telomerase-positive cell lines and the two telomerase negative cell lines were found to be hypermethylated, suggesting that the methylation observed may occur during cell line establishment. In conclusion, this study shows that hTERC expression is indeed regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression
Keywords
Antimetabolites,Antineoplastic/pharmacology/Azacitidine/analogs & derivatives/Cell Division/Cell Line/DNA Methylation/Gene Expression Regulation,Neoplastic/Hela Cells/Humans/Neoplasms/metabolism/Polymorphism,Genetic/Promoter Regions (Genetics)/Protein Conformation/Rna/Reverse Transcriptase Polymerase Chain Reaction/Sarcoma/Sulfites/Telomerase/Tumor Cells,Cultured
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 19:34
Last modification date
25/09/2019 7:10
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