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A genetic mouse model for metastatic lung cancer with gender differences in survival

Oncogene volume 26, pages 6896–6904 (2007)Cite this article

Abstract

Lung cancer is a devastating disease with poor prognosis. The design of better therapies for lung cancer patients would be greatly aided by good mouse models that closely resemble the human disease. Unfortunately, current models for lung adenocarcinoma are inadequate due to the absence of metastases. In this study, we incorporated both K-ras and p53 missense mutations into the mouse genome and established a more faithful genetic model for human lung adenocarcinoma, the most common type of lung cancer. Mice with both mutations developed advanced lung adenocarcinomas that were highly aggressive and metastasized to multiple intrathoracic and extrathoracic sites in a pattern similar to that of human lung cancer. These mice also showed a gender difference in cancer-related death. Additionally, the presence of both mutations induced pleural mesotheliomas in 23% of these mice. This mouse model recapitulates the metastatic nature of human lung cancer and will be invaluable to further probe the molecular basis of metastatic lung cancer and for translational studies.

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Acknowledgements

This study was supported by a grant from the Department of Defense, DAMD17-01-1-0689 and the Cancer Center Support Grant CA16672 from the NIH. We thank Tyler Jacks for the K-rasLA1/+ mice.

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Authors and Affiliations

  1. Department of Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    S Zheng & G Lozano

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    A K El-Naggar

  3. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    E S Kim & J M Kurie

  4. Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA

    S Zheng & G Lozano

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  1. S Zheng
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  2. A K El-Naggar
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  5. G Lozano
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Correspondence to G Lozano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Zheng, S., El-Naggar, A., Kim, E. et al. A genetic mouse model for metastatic lung cancer with gender differences in survival. Oncogene 26, 6896–6904 (2007). https://doi.org/10.1038/sj.onc.1210493

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