Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model
Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model
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DOI：
10.1016/s1535-6108(03)00220-4
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发表时间：
2003-09-01
期刊：
影响因子：
50.3
通讯作者：
Berns, A
中科院分区：
文献类型：
--
作者：
Meuwissen, R;Linn, SC;Berns, A
小细胞肺癌（SCLC）是一种高度侵袭性的人类肿瘤，死亡率超过95%。其个体发生和分子发病机制仍然知之甚少。我们建立了一个神经内分泌（NE）肺肿瘤的小鼠模型，通过在小鼠肺上皮细胞中的Rb 1和Trp53的条件性失活。携带Rb 1和Trp53条件等位基因的小鼠发生侵袭性肺肿瘤的发病率高，与SCLC具有惊人的形态学和免疫表型相似性。这些肿瘤中的大多数，我们命名为MSCLC（小鼠小细胞肺癌），弥漫性扩散通过肺，并引起肺外转移。在我们的模型中，Rb 1和p53的失活是SCLC发病的先决条件。
Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.