Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma
Loss of Rho function in the thymus is accompanied by the development of thymic lymphoma
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DOI：
10.1038/sj.onc.1203259
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发表时间：
2000-01-06
期刊：
影响因子：
8
通讯作者：
Cantrell, DA
中科院分区：
文献类型：
--
作者：
Cleverley, SC;Costello, PS;Cantrell, DA
模型细胞系的原位研究表明，GTPase Rho参与控制多种细胞反应，包括控制肌动蛋白细胞骨架和调节细胞周期进程。也有报道称，通过致癌Ras的成纤维细胞转化需要完整的Rho信号。一种用于研究Rho功能的宝贵工具是源自热芽梭菌的细菌毒素C3转移酶。C3转移酶在其效应域中核糖化Rho，从而消除与下游效应物的相互作用。我们之前报道了在胸腺细胞特异性Ick启动子的控制下使用C3转移酶来探索Rho在T细胞生物学中的作用。引人注目的是，Ick-C3小鼠在4到8个月大时患上了侵袭性恶性胸腺淋巴母细胞淋巴瘤。这些研究表明，Rho功能的丧失与淋巴样细胞转化的易感性有关。抑制Rho功能已被认为是治疗ras转化肿瘤的一种治疗策略，在T细胞室缺乏功能性Rho的小鼠中发生的淋巴瘤表明，这种策略需要谨慎使用。
In situ studies in model cell lines have implicated the GTPase Rho in the control of diverse cellular responses including the control of the actin cytoskeleton and the regulation of cell cycle progression. It is also reported that the transformation of fibroblasts via oncogenic Ras requires intact Rho signalling. An invaluable tool used to investigate Rho function is the bacterial toxin C3 transferase derived from Clostridium hotulinum. C3 transferase ribosylates Rho in its effector domain thereby abolishing interaction with downstream effecters. We have previously reported the use of C3 transferase under the control of the thymocyte specific Ick promoter to explore the role of Rho in T cell biology. Strikingly, Ick-C3 mice develop aggressive malignant thymic lymphoblastic lymphomas between 4 and 8 months of age. These studies reveal that loss of Rho function is associated with prediposition to lymphoid cell transformation. Inhibition of Rho function has been suggested as a therapeutic strategy for treatment of Ras-transformed tumours, The development of lymphomas in mice devoid of functional Rho in their T cell compartment shows that such a strategy would need to be used with caution.