Metastasis-associated protein 1 transgenic mice: a new model of spontaneous B-cell lymphomas.
Metastasis-associated protein 1 transgenic mice: a new model of spontaneous B-cell lymphomas.
复制标题
转移相关蛋白 1 转基因小鼠：自发性 B 细胞淋巴瘤的新模型。
DOI：
10.1158/0008-5472.can-07-0748
复制
发表时间：
2007
期刊：
影响因子：
11.2
通讯作者：
Kumar
中科院分区：
文献类型：
--
作者：
Bagheri-Yarmand,Rozita;Balasenthil,Seetharaman;Gururaj,AnupamaE;Talukder,AmjadH;Wang,Yui-Hsi;Lee,JuHan;Kim,YoungSik;Zhang,Xinaglan;Jones,DanielM;Medeiros,LJeffrey;Stephens,LClifton;Liu,Yong-Jun;Lee,Norman;Kim,Insun;Kumar
转移相关蛋白1（MTA 1）是核重塑复合物的一种成分，也是MTA家族的创始同源物，它与转移有关，但目前缺乏动物模型系统中明确的致病证据。在此，我们发现转基因小鼠中MTA 1过表达伴随自发性B细胞淋巴瘤包括弥漫性大B细胞淋巴瘤（DLBCL）的高发病率。来自MTA 1-TG小鼠的淋巴细胞和淋巴瘤细胞是过度增殖的。淋巴瘤是可移植的，克隆起源的，其特征在于下调p27 Kip 1以及上调Bcl 2和细胞周期蛋白D1。这些小鼠研究的意义通过显示来自人类的DLBCL中MTA 1的广泛上调的证据来确立。这些发现揭示了以前未认识到的作用，MTA 1途径在自发性B细胞淋巴瘤的发展，并提供了一个潜在的治疗靶点在B细胞淋巴瘤。这些观察结果表明，MTA 1-TG小鼠代表了与高肿瘤发生率相关的自发性DLBCL的新模型，并可用于治疗干预研究。[Cancer Res 2007;67（15）：7062-7]
Metastasis-associated protein 1 (MTA1), a component of the nuclear remodeling complex and the founding homologue of the MTA family, has been implicated in metastasis, but definitive causative evidence in an animal model system is currently lacking. Here, we show that MTA1 overexpression in transgenic mice is accompanied by a high incidence of spontaneous B cell lymphomas including diffuse large B cell lymphomas (DLBCL). Lymphocytes and lymphoma cells from MTA1-TG mice are hyperproliferative. Lymphomas were transplantable and of clonal origin and were characterized by down-regulation of p27Kip1 as well as up-regulation of Bcl2 and cyclin D1. The significance of these murine studies was established by evidence showing a widespread up-regulation of MTA1 in DLBCL from humans. These findings reveal a previously unrecognized role for the MTA1 pathway in the development of spontaneous B cell lymphomas, and offer a potential therapeutic target in B cell lymphomas. These observations suggest that MTA1-TG mice represent a new model of spontaneous DLBCL associated with high tumor incidence and could be used for therapeutic intervention studies. [Cancer Res 2007;67(15):7062–7]