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利用致癌性K-ras的条件性表达分析肺肿瘤的起始和进展

Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras.

作者信息

Jackson E L, Willis N, Mercer K, Bronson R T, Crowley D, Montoya R, Jacks T, Tuveson D A

机构信息

Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

Genes Dev. 2001 Dec 15;15(24):3243-8. doi: 10.1101/gad.943001.

DOI:10.1101/gad.943001
PMID:11751630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC312845/
Abstract

Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of a recombinant adenovirus expressing Cre recombinase (AdenoCre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation. Through the ability to synchronize tumor initiation in these mice, we have been able to characterize the stages of tumor progression. Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma.

摘要

肺腺癌是肺癌最常见的形式,但这种肿瘤类型的起源细胞和进展阶段尚未完全清楚。我们构建了一种携带致癌性K-ras条件性激活等位基因的小鼠肺腺癌新模型。在此我们表明,利用表达Cre重组酶的重组腺病毒(腺病毒Cre)在小鼠肺中诱导K-ras G12D表达,能够控制肿瘤起始的时间和多发性。通过同步这些小鼠肿瘤起始的能力,我们得以描绘肿瘤进展的阶段。特别重要的是,该系统已导致鉴定出一种对肺腺癌发展有贡献的新细胞类型。

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本文引用的文献

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Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.K-ras癌基因的体细胞激活会导致小鼠早发性肺癌。
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Pulmonary preinvasive neoplasia.肺浸润前肿瘤
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Surfactant protein C expression in urethane-induced murine pulmonary tumors.表面活性蛋白C在氨基甲酸乙酯诱导的小鼠肺部肿瘤中的表达
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Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5037-42. doi: 10.1073/pnas.96.9.5037.
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Increasing complexity of Ras signaling.Ras信号传导的复杂性不断增加。
Oncogene. 1998 Sep 17;17(11 Reviews):1395-413. doi: 10.1038/sj.onc.1202174.
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Molecular comparison of human and mouse pulmonary adenocarcinomas.人类与小鼠肺腺癌的分子比较。
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8
Incorporation of adenovirus in calcium phosphate precipitates enhances gene transfer to airway epithelia in vitro and in vivo.腺病毒掺入磷酸钙沉淀物中可增强体外和体内向气道上皮细胞的基因转移。
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Cytodifferentiation of atypical adenomatous hyperplasia and bronchioloalveolar lung carcinoma: immunohistochemical and ultrastructural studies.非典型腺瘤样增生与细支气管肺泡肺癌的细胞分化:免疫组织化学与超微结构研究
Virchows Arch. 1997 Dec;431(6):415-24. doi: 10.1007/s004280050118.
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K-ras is an essential gene in the mouse with partial functional overlap with N-ras.K-ras是小鼠中的一个必需基因,与N-ras存在部分功能重叠。
Genes Dev. 1997 Oct 1;11(19):2468-81. doi: 10.1101/gad.11.19.2468.