Enhanced T cell lymphoma in NOD.Stat5b transgenic mice is caused by hyperactivation of Stat5b in CD8+ thymocytes.
Enhanced T cell lymphoma in NOD.Stat5b transgenic mice is caused by hyperactivation of Stat5b in CD8+ thymocytes.
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DOI：
10.1371/journal.pone.0056600
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
She JX
中科院分区：
文献类型：
--
作者：
Chen B;Yi B;Mao R;Liu H;Wang J;Sharma A;Peiper S;Leonard WJ;She JX
信号转导和转录激活因子（STAT）蛋白的激活可能是其致癌功能的关键，如在过表达Stat 5 b组成型激活形式的转基因（TG）小鼠中发生B细胞淋巴瘤/白血病所证明的。然而，在过度表达野生型Stat 5 b（B6.Stat5bTg）的B6转基因小鼠中观察到低的CD 8 + T细胞淋巴瘤发生率，尽管未检测到Stat 5 b磷酸化，并且通过免疫或引入TCR转基因显著增强淋巴瘤发生率。在这里，我们报告野生型Stat 5 b转基因导致非肥胖糖尿病（NOD）背景下CD 8 + T细胞淋巴母细胞淋巴瘤的加速和高发病率（74%）。与B6.Stat5bTg小鼠相反，转基因NOD（NOD.Stat5bTg）小鼠中的Stat 5 b在CD 8+胸腺细胞中选择性和进行性磷酸化。Stat 5磷酸化还导致许多与肿瘤发生相关的基因上调。用癌症化学预防剂芹菜素和黄腐酚治疗NOD.Stat5bTg小鼠，通过减少NOD.Stat5bTg小鼠中Stat 5磷酸化和基因上调，有效地阻断了淋巴瘤的发生。这些结果表明，NOD的遗传背景是至关重要的Stat 5 b介导的淋巴瘤的发生，通过调节Stat 5超活化。NOD.Stat5bTg小鼠是研究淋巴瘤发生的分子机制和测试新的化学预防策略的极好模型。
Activation of signal transducers and activators of transcription (STAT) proteins may be critical to their oncogenic functions as demonstrated by the development of B-cell lymphoma/leukemia in transgenic (TG) mice overexpressing a constitutively activated form of Stat5b. However, low incidence of CD8+ T cell lymphoma was observed in B6 transgenic mice overexpressing a wild-type Stat5b (B6.Stat5bTg) despite of undetectable Stat5b phosphorylation and the rate of lymphomagenesis was markedly enhanced by immunization or the introduction of TCR transgenes. Here, we report that the wild-type Stat5b transgene leads to the acceleration and high incidence (74%) of CD8+ T cell lymphoblastic lymphomas in the non-obese-diabetic (NOD) background. In contrast to the B6.Stat5bTg mice, Stat5b in transgenic NOD (NOD.Stat5bTg) mice is selectively and progressively phosphorylated in CD8+ thymocytes. Stat5 phosphorylation also leads to up-regulation of many genes putatively relevant to tumorigenesis. Treatment of NOD.Stat5bTg mice with cancer chemopreventive agents Apigenin and Xanthohumol efficiently blocked lymphomagenesis through reduction of Stat5 phosphorylation and genes up-regulated in the NOD.Stat5bTg mice. These results suggest that NOD genetic background is critical to the Stat5b-mediated lymphomagenesis through regulation of Stat5 hyperactivation. NOD.Stat5bTg mouse is an excellent model for studying the molecular mechanisms underlying lymphomagenesis and testing novel chemoprevention strategies.
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DOI：
10.1084/jem.180.2.631
发表时间：
1994-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hathcock KS;Laszlo G;Pucillo C;Linsley P;Hodes RJ
通讯作者：
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影响因子：
32.4
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通讯作者：
Kelly, John A.
影响因子：
4.4
作者：
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通讯作者：
Farrar, MA
影响因子：
4.4
作者：
Kelly, J;Spolski, R;Leonard, WJ
通讯作者：
Leonard, WJ