Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis

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Title: Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis
Author: Armanios, Mary; Qi, Ling; Strong, Margaret A.; Karim, Baktiar O.; Greider, Carol W.; Huso, David L.
Abstract: To examine the role of ataxia-telangiectasia mutated (Atm) in telomere function, we generated Atm and telomerase null mice (Atm(-/-) mTR(-/-) iG6 mice). These mice exhibited increased germ cell death and chromosome fusions compared with either Atm(-/-) or mTR(-/-) iG6 mice. Furthermore, the Atm(-/-) mTR(--) iG6 mice had a delayed onset and reduced incidence of thymic lymphoma compared with Atm(-/-) mice. The tumors in the Atm(-/-) mTR(-/-) iG6 mice showed increased apoptosis and anaphase bridges. Finally, lymphomas from Atm(-/-) mTR(-/-) iG6 mice were derived from CD8 immature, single-positive T cells, whereas Atm(-/-) lymphomas were from CD4(+)CD8(+) double-positive T cells. We propose that Atm protects short telomeres and that Atm deficiency cooperates with short telomeres, leading to increased cell death, decreased tumorigenesis, and increased overall survival.
URI: http://jhir.library.jhu.edu/handle/1774.2/33535
Date: 2003-12-01
Citation: Qi, Ling, et al. "Short telomeres and ataxia-telangiectasia mutated deficiency cooperatively increase telomere dysfunction and suppress tumorigenesis" Cancer Research 63, 8188-8196. December 1, 2003
Subject: Telomere/genetics
Tumor Suppressor Proteins
Cell Transformation, Neoplastic
Telomere/physiology
Telomerase/deficiency

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