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Molecular and Cellular Biology, May 2004, p. 4275-4293, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4275-4293.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Andrés Canela,1 Juan Martín-Caballero,2 Juana M. Flores,3 and María A. Blasco1*

Telomeres and Telomerase Group, Molecular Oncology Program,1 Biotechnology Program, Spanish National Cancer Centre (CNIO), 28029 Madrid,2 Department of Animal Pathology II, Universidad Complutense de Madrid, 28040 Madrid, Spain3

Received 20 October 2003/ Returned for modification 23 November 2003/ Accepted 20 January 2004

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.

* Corresponding author. Mailing address: Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, E-38029 Madrid, Spain. Phone: 34 917328031. Fax: 34 917328028. E-mail: mblasco{at}cnio.es.

Molecular and Cellular Biology, May 2004, p. 4275-4293, Vol. 24, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.10.4275-4293.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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