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DNA DYNAMICS AND CHROMOSOME STRUCTURE

Constitutive Expression of Tert in Thymocytes Leads to Increased Incidence and Dissemination of T-Cell Lymphoma in Lck-Tert Mice

Andrés Canela, Juan Martín-Caballero, Juana M. Flores, María A. Blasco
Andrés Canela
1Telomeres and Telomerase Group, Molecular Oncology Program
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Juan Martín-Caballero
2Biotechnology Program, Spanish National Cancer Centre (CNIO), 28029 Madrid
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Juana M. Flores
3Department of Animal Pathology II, Universidad Complutense de Madrid, 28040 Madrid, Spain
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María A. Blasco
1Telomeres and Telomerase Group, Molecular Oncology Program
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  • For correspondence: mblasco@cnio.es
DOI: 10.1128/MCB.24.10.4275-4293.2004
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ABSTRACT

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.

  • Copyright © 2004 American Society for Microbiology
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Constitutive Expression of Tert in Thymocytes Leads to Increased Incidence and Dissemination of T-Cell Lymphoma in Lck-Tert Mice
Andrés Canela, Juan Martín-Caballero, Juana M. Flores, María A. Blasco
Molecular and Cellular Biology Apr 2004, 24 (10) 4275-4293; DOI: 10.1128/MCB.24.10.4275-4293.2004

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Constitutive Expression of Tert in Thymocytes Leads to Increased Incidence and Dissemination of T-Cell Lymphoma in Lck-Tert Mice
Andrés Canela, Juan Martín-Caballero, Juana M. Flores, María A. Blasco
Molecular and Cellular Biology Apr 2004, 24 (10) 4275-4293; DOI: 10.1128/MCB.24.10.4275-4293.2004
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KEYWORDS

Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Lymphoma, T-Cell
T-Lymphocytes
telomerase

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