一种用于恶性间皮瘤的条件性小鼠模型。

A conditional mouse model for malignant mesothelioma.

作者信息

Jongsma Johan, van Montfort Erwin, Vooijs Marc, Zevenhoven John, Krimpenfort Paul, van der Valk Martin, van de Vijver Marc, Berns Anton

机构信息

Department of Molecular Genetics, Cancer Genomics Centre, Centre for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

出版信息

Cancer Cell. 2008 Mar;13(3):261-71. doi: 10.1016/j.ccr.2008.01.030.

DOI:10.1016/j.ccr.2008.01.030

PMID:18328429

Abstract

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;Ink4a/Arf 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;Ink4a/Arf 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.

摘要

恶性间皮瘤是一种毁灭性疾病，与2型神经纤维瘤病（NF2）缺失以及影响RB和P53通路的基因损伤有关。我们在小鼠胸腔的间皮衬里引入了类似的损伤。在Nf2;Ink4a/Arf和Nf2;p53条件性敲除小鼠中，间皮瘤的发病率很高，中位生存时间分别约为30周和20周。小鼠间皮瘤与人类恶性间皮瘤极为相似。与条件性Nf2;p53小鼠相比，条件性Nf2;Ink4a/Arf小鼠的胸膜侵犯增加。有趣的是，在后者小鼠中Ink4a缺失后，中位生存时间显著缩短，所有肿瘤均具有高度侵袭性，这表明Ink4a缺失在很大程度上导致了恶性间皮瘤不良的临床结局。