Moderate expression of TRF2 in the hematopoietic system increases development of large cell blastic T-cell lymphomas.
Moderate expression of TRF2 in the hematopoietic system increases development of large cell blastic T-cell lymphomas.
复制标题
DOI：
10.18632/aging.100015
复制
发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Karlseder J
中科院分区：
文献类型：
--
作者：
Begemann S;Galimi F;Karlseder J
端粒重复序列结合因子2（TRF 2） 在保护染色体末端中起核心作用， 启动DNA损伤级联反应。TRF 2过表达 已被建议在小鼠中诱导肿瘤发展，并且TRF 2水平 在人类肿瘤中的含量增加。在这里，我们测试是否适度 TRF 2在造血系统中的表达导致癌症发展 在老鼠。将TRF 2和GFP-TRF 2融合蛋白引入到 造血前体，并进行功能测试。TRF 2过表达 C57 BL/6 J受体细胞整合入造血系统 小鼠和动物被置于肿瘤观察中。发展中的增长 在第二受体动物中观察到T细胞淋巴瘤，然而， TRF 2转基因的过表达在小鼠中不再检测到。 肿瘤的肿瘤的特点是大细胞母细胞性T细胞 淋巴瘤和显示的迹象，基因组不稳定的证据是染色体 融合然而，TRF 2过表达的淋巴瘤发生率与TRF 2表达的淋巴瘤发生率相关。 动物的表达较低，表明TRF 2并不是显性癌基因 在使用的系统中。
The telomeric repeat binding factor 2 (TRF2) plays a central role in the protection of chromosome ends by inhibiting telomeres from initiating a DNA damage cascade. TRF2 overexpression has been suggested to induce tumor development in the mouse, and TRF2 levels have been found increased in human tumors. Here we tested whether moderate expression of TRF2 in the hematopoietic system leads to cancer development in the mouse. TRF2 and a GFP-TRF2 fusion protein were introduced into hematopoietic precursors, and tested for function. TRF2 overexpressing cells were integrated into the hematopoietic system of C57BL/6J recipient mice, and animals were put on tumor watch. An increase in the development of T-cell lymphomas was observed in secondary recipient animals, however, overexpression of the TRF2 transgene was not detectable anymore in the tumors. The tumors were characterized as large cell blastic T-cell lymphomas and displayed signs of genome instability as evidenced by chromosome fusions. However, the rate of lymphoma development in TRF2-overexpressing animals was low, suggesting the TRF2 does not serve as a dominant oncogene in the system used.
登录
查看更多内容
影响因子：
30.8
作者：
Muñoz, P;Blanco, R;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
9.2
作者：
Smogorzewska, A;Karlseder, J;de Lange, T
通讯作者：
de Lange, T
影响因子：
64.5
作者：
Barlow, C;Hirotsune, S;WynshawBoris, A
通讯作者：
WynshawBoris, A
影响因子：
4.8
作者：
Opresko, PL;von Kobbe, C;Bohr, VA
通讯作者：
Bohr, VA
影响因子：
9.8
作者：
Karlseder J;Hoke K;Mirzoeva OK;Bakkenist C;Kastan MB;Petrini JH;de Lange T
通讯作者：
de Lange T