Abstract
The onset of human lung cancer occurs through sequential mutations in oncogenes and tumor suppressor genes. Mutations in K-Ras play a prominent role in human non-small cell lung cancer. We have developed a mouse lung tumor model in which K-Ras can be sporadically activated through Cre-lox mediated somatic recombination. Adenoviral mediated delivery of Cre recombinase in lung epithelial cells gave rise to rapid onset of tumorigenesis, yielding pulmonary adenocarcinomas with 100% incidence after a short latency. The lung tumor lesions shared many features with human non-small cell lung cancer. Our data show that sporadic expression of the K-Ras oncogene is sufficient to elicit lung tumorigenesis. Therefore this model has many advantages over conventional transgenic models used thus far.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / etiology*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenoviridae / genetics
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Alleles
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Animals
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Carcinoma, Non-Small-Cell Lung / etiology*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Disease Models, Animal*
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Genes, Reporter
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Genetic Vectors
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Integrases / genetics*
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Integrases / metabolism
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Lung Neoplasms / etiology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Transgenic
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Oncogene Protein p21(ras) / biosynthesis
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Oncogene Protein p21(ras) / genetics*
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RNA, Neoplasm / biosynthesis
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Recombination, Genetic
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Viral Proteins / genetics*
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Viral Proteins / metabolism
Substances
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RNA, Neoplasm
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Viral Proteins
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Cre recombinase
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Integrases
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Oncogene Protein p21(ras)