A conditional mouse model for malignant mesothelioma
A conditional mouse model for malignant mesothelioma
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DOI：
10.1016/j.ccr.2008.01.030
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发表时间：
2008-03-01
期刊：
影响因子：
50.3
通讯作者：
Berns, Anton
中科院分区：
文献类型：
--
作者：
Jongsma, Johan;van Montfort, Erwin;Berns, Anton
恶性间皮瘤是一种毁灭性的疾病，它与2型神经纤维瘤病（NF 2）的丢失和影响RB和P53通路的遗传病变有关。我们在小鼠胸腔的间皮衬里中引入了类似的病变。间皮瘤在Nf 2; Ink 4alArf和Nf 2;p53条件性敲除小鼠中以高发病率发展，中位存活时间分别为约30周和20周。小鼠间皮瘤与人类恶性间皮瘤非常相似。与条件性Nf 2;p53小鼠相比，条件性Nf 2; Ink 4alArf小鼠显示增加的胸膜侵袭。有趣的是，在后者小鼠中Ink 4a损失后，中位存活率显著降低，并且所有肿瘤都是高度侵袭性的，这表明Ink 4a损失实质上导致恶性间皮瘤的不良临床结果。
Malignant mesothelioma is a devastating disease that has been associated with loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53 pathways. We introduced similar lesions in the mesothelial lining of the thoracic cavity of mice. Mesothelioma developed at high incidence in Nf2;Ink4alArf and Nf2;p53 conditional knockout mice with median survival times of approximately 30 and 20 weeks, respectively. Murine mesothelioma closely mimicked human malignant mesothelioma. Conditional Nf2;Ink4alArf mice showed increased pleural invasion compared to conditional Nf2;p53 mice. Interestingly, upon Ink4a loss in the latter mice median survival was significantly reduced and all tumors were highly invasive, suggesting that Ink4a loss substantially contributes to the poor clinical outcome of malignant mesothelioma.