Immortalization and transformation of primary human airway epithelial cells by gene transfer
Immortalization and transformation of primary human airway epithelial cells by gene transfer
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DOI：
10.1038/sj.onc.1205550
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发表时间：
2002-07-04
期刊：
影响因子：
8
通讯作者：
Hahn, WC
中科院分区：
文献类型：
--
作者：
Lundberg, AS;Randell, SH;Hahn, WC
癌细胞发展的一个关键步骤是获得无限的复制寿命，这个过程被称为永生化。迄今为止，设计用于研究离体细胞转化的实验模型系统依赖于通过化学或物理诱变剂处理而永生化的细胞亚群的体外选择以及稀有克隆变体的选择。在这项研究中，我们描述了直接永生化的原代人气道上皮细胞通过连续引入猿猴病毒40早期区和端粒酶催化亚基hTERT。以这种方式永生化的细胞现在对引入的H-ras或K-ras癌基因的恶性转化有反应。这些永生化的人气道上皮细胞，已通过逐步引入遗传改变，提供了一种新的实验模型系统，进一步研究气道上皮细胞的生物学和解剖肺癌发病机制的分子基础。
One critical step in the development of a cancerous cell is its acquisition of an unlimited replicative lifespan, the process termed immortalization. Experimental model systems designed to study cellular transformation ex vivo have relied to date on the in vitro selection of a subpopulation of cells that have become immortalized through treatment with chemical or physical mutagens and the selection of rare clonal variants. In this study, we describe the direct immortalization of primary human airway epithelial cells through the successive introduction of the Simian Virus 40 Early Region and the telomerase catalytic subunit hTERT. Cells immortalized in this way are now responsive to malignant transformation by an introduced H-ras or K-ras oncogene. These immortalized human airway epithelial cells, which have been created through the stepwise introduction of genetic alterations, provide a novel experimental model system with which to study further the biology of the airway epithelial cell and to dissect the molecular basis of lung cancer pathogenesis.