Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells
Open accessAbstract
In mammals, molecular mechanisms and factors involved in the tight regulation of telomerase expression and activity are still largely undefined. In this study, we provide evidence for a role of estrogens and their receptors in the transcriptional regulation of hTERT, the catalytic subunit of human telomerase and, consequently, in the activation of the enzyme. Through a computer analysis of the hTERT 5'-flanking sequences, we identified a putative estrogen response element (ERE) which was capable of binding in vitro human estrogen receptor alpha (ERalpha). In vivo DNA footprinting revealed specific modifications of the ERE region in ERalpha-positive but not ERalpha-negative cells upon treatment with 17beta-estradiol (E2), indicative of estrogen-dependent chromatin remodelling. In the presence of E2, transient expression of ERalpha but not ERbeta remarkably increased hTERT promoter activity, and mutation of the ERE significantly reduced this effect. No telomerase activity was detected in human ovary epithelial cells grown in the absence of E2, but the addition of the hormone induced the enzyme within 3 h of treatment. The expression of hTERT mRNA and protein was induced in parallel with enzymatic activity. This prompt estrogen modulation of telomerase activity substantiates estrogen-dependent transcriptional regulation of the hTERT gene. The identification of hTERT as a target of estrogens represents a novel finding which advances the understanding of telomerase regulation in hormone-dependent cells and has implications for a potential role of hormones in their senescence and malignant conversion.
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Estrogen activates hTERT transcription through binding of ligand-activated ERα to the estrogen-responsive element in the hTERT promoter.
“We and other groups found that estrogen activates hTERT transcription via binding of ligand-activated estrogen receptor-α (ERα) to the estrogen-responsible element (ERE) in the hTERT promoter.(29,30)”
From Understanding and exploiting <i>hTERT</i> promoter regulation for diagnosis and treatment of human cancers (2008) · cites this paper as [30]
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- Authors
- Misiti, S., Nanni, S., Fontemaggi, G., Cong, Y.-S., Wen, J., Hirte, H. W., Piaggio, G., Sacchi, A., Pontecorvi, A., Bacchetti, S., & Farsetti, A.
- Affiliations
- Instituto Nazionale Tumori Regina Elena (IT)
- Department of Pathology and Molecular Medicine
- McMaster University (CA)
- Università Cattolica del Sacro Cuore (IT)
- National Academies of Sciences, Engineering, and Medicine (US)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-06
- Volume
- 20
- Issue
- 11
- Pages
- 3764-3771
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85692
- OpenAlex
- W2145305345
- Cited by
- 254
- References
- 52
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 12
- FWCI
- 10.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- hTERT, telomerase, estrogen, estrogen receptor alpha, estrogen receptor beta, estradiol, estrogen response element, transcriptional regulation, telomerase activation, chromatin remodeling, DNA footprinting, telomerase regulation, cellular senescence, malignant transformation
- MeSH terms
- Animals, Base Sequence, Cell Line, DNA-Binding Proteins, Epithelial Cells, Estradiol, Female, HeLa Cells, Humans, Ligands, Molecular Sequence Data, Ovary, Promoter Regions, Genetic, Receptors, Estrogen, Recombinant Fusion Proteins, RNA, Transcription, Genetic, Gene Expression Regulation, Enzymologic, 3T3 Cells, DNA, Complementary, Telomerase, Catalytic Domain, Estrogen Receptor alpha, Estrogen Receptor beta, Mice
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