Constitutive Expression of Tert in Thymocytes Leads to Increased Incidence and Dissemination of T-Cell Lymphoma in Lck-Tert Mice
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Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.
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Overexpression of mouse telomerase reverse transcriptase catalytic subunit induces a variety of malignancies.
“Overexpression of the mouse telomerase reverse transcriptase catalytic subunit (mTERTcs) has been shown to induce a variety of malignancies64–66.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [64]
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- Authors
- Canela, A., Martín-Caballero, J., Flores, J. M., & Blasco, M. A.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Biotechnology Program, Spanish National Cancer Centre (CNIO), 28029 Madrid
- Universidad Complutense de Madrid (ES)
- Telomeres and Telomerase Group, Molecular Oncology Program
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-05-01
- Volume
- 24
- Issue
- 10
- Pages
- 4275-4293
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC400466
- OpenAlex
- W2101446599
- Cited by
- 90
- References
- 33
- Citations by year
- 2024: 2 · 2023: 4 · 2021: 3 · 2020: 3 · 2018: 2 · 2017: 2 · 2016: 8 · 2015: 2 · 2014: 2 · 2013: 7 · 2012: 9
- FWCI
- 4.52
- 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)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- telomerase reverse transcriptase, T-cell lymphoma, thymocytes, lymphoma dissemination, telomere length, telomere capping, chromosomal instability, DNA damage response, constitutive expression, mouse tumor model
- MeSH terms
- Animals, Base Sequence, Disease Models, Animal, DNA Damage, DNA-Binding Proteins, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Promoter Regions, Genetic, RNA, Messenger, T-Lymphocytes, Gene Expression, Lymphoma, T-Cell, Telomere, DNA, Complementary, Telomerase, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Mice
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