Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice
Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice
复制标题
DOI：
10.1128/mcb.24.10.4275-4293.2004
复制
发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Canela, A;Martín-Caballero, J;Blasco, MA
在这里，我们描述了一种新的小鼠模型，其端粒酶催化亚基（Tert）的组成表达靶向胸腺细胞和外周T细胞（Lck-Tert小鼠）。两个独立的Lck-Tert小鼠系自发性t细胞淋巴瘤的发生率高于。相应的年龄匹配的野生型对照，表明Tert的组成性表达促进淋巴瘤。有趣的是，Lck-Tert小鼠的t细胞淋巴瘤比野生型对照小鼠更具有播散性，并且影响淋巴组织和非淋巴组织，而年龄匹配的野生型对照小鼠的非淋巴组织从未受到淋巴瘤的影响。重要的是，Tert组成表达在促进肿瘤进展和传播中的作用独立于端粒酶在端粒长度维持中的作用，因为Lck-Tert和野生型胸腺细胞的端粒长度分布在单细胞基础上是相同的。最后，在Lck-Tert原代胸腺细胞中，Tert的组成性表达并未干扰端粒盖帽，尽管与对照组相比，它在γ辐射下导致Lck-Tert原代淋巴细胞的染色体不稳定性更大，这表明Tert过表达可能会干扰细胞对DNA损伤的反应。
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.