The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity
Open accessAbstract
DNA methylation is an epigenetic process involved in embryonic development, differentiation and aging. It is 1 of the mechanisms resulting in gene silencing in carcinogenesis, especially in tumor suppressor genes (e.g., p16, Rb). Telomerase, the DNA polymerase adding TTAGGG repeats to the chromosome end, is involved in the regulation of the replicative life span by maintaining telomere length. This enzyme is activated in germ and stem cells, repressed in normal somatic cells and reactivated in a large majority of tumor cells. The promoter region of the hTERT gene, encoding for the catalytic subunit of human telomerase, has been located in a CpG island and may therefore be regulated at least in part by DNA methylation. We analyzed the methylation status of 27 CpG sites within the hTERT promoter core region by methylation‐sensitive single‐strand conformation analysis (MS‐SSCA) and direct sequencing using bisulfite‐modified DNA in 56 human tumor cell lines, as well as tumor and normal tissues from different organs. A positive correlation was observed among hypermethylation of the hTERT promoter, hTERT mRNA expression and telomerase activity (p < 0.00001). Furthermore, this correlation was confirmed in normal tissues where hypermethylation of the hTERT promoter was found exclusively in hTERT‐expressing telomerase‐positive samples and was absent in telomerase‐negative samples (p < 0.00002). Since tumor tissues contain also nonneoplastic stromal elements, we performed microdissection to allow confirmation that the hTERT promoter methylation truly occurred in tumor cells. Our results suggest that methylation may be involved in the regulation of hTERT gene expression. To our knowledge, this is the first gene in which methylation of its promoter sequence has been found to be positively correlated with gene expression. © 2002 Wiley‐Liss, Inc.
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“There is a strong correlation between hTERT expression and TA, and recent studies have linked hTERT promoter hypermethylation to CRC and other cancer types [206].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [206]
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The relationship between COPD and lung cancer
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Sulforaphane Causes Epigenetic Repression of hTERT Expression in Human Breast Cancer Cell Lines
Meeran, S. M., Patel, S. N., & Tollefsbol, T. O. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011457 · Cited by 372
Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers
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TERT—Regulation and Roles in Cancer Formation
Dratwa, M., Wysoczańska, B., Łacina, P., Kubik, T., & Bogunia‐Kubik, K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.589929 · Cited by 331
Metadata
- Authors
- Guilleret, I., Yan, P., Grange, F., Braunschweig, R., Bosman, F. T., & Benhattar, J.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Benhattar, Jean
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2002-08-29
- Volume
- 101
- Issue
- 4
- Pages
- 335-341
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2055902044
- Cited by
- 260
- References
- 44
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 12 · 2020: 18 · 2019: 13 · 2018: 12 · 2017: 12 · 2016: 19 · 2015: 18 · 2014: 5 · 2013: 12 · 2012: 8
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- hTERT, telomerase, promoter hypermethylation, DNA methylation, CpG islands, telomerase activity, gene expression regulation, tumor suppressor, gene silencing, cancer cell lines, telomere length
- MeSH terms
- DNA-Binding Proteins, Humans, Neoplasms, Promoter Regions, Genetic, RNA, Messenger, Tumor Cells, Cultured, Gene Expression Regulation, Enzymologic, Polymorphism, Single-Stranded Conformational, Telomerase, DNA Methylation
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