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A mouse model for tumor progression of lung cancer in ras and p53 transgenic mice

Oncogene volume 25, pages 1277–1280 (2006)Cite this article

Abstract

Although ras and p53 are the most commonly found oncogene and tumor suppressor gene, respectively, in human cancers, their collective roles in tumor progression have yet to be defined in animal models. Here, we demonstrated the synergistic effect between ras and p53 in promoting tumor progression during lung tumorigenesis using bitransgenic mice. Mice with a heterozygous knockout of K-ras (K-raswt/ko) were mated to p53 transgenic mice (p53val135/wt) in lung tumorigenesis (K-raswt/ko × p53val135/wt). F1 mice exhibited a significant increase in lung tumor load (tumor multiplicity × tumor volume) when compared to those seen in either K-raswt/ko mice or p53val135/wt mice alone. Furthermore, over 50% of the lung tumors were lung adenocarcinomas in bitransgenic mice compared to only 3% in wild-type mice. Alterations of ras and p53 appear to promote the development of lung adenocarcinomas. These results provide the in vivo experimental evidence of synergistic interactions of ras and p53 in lung tumor progression.

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Acknowledgements

We are grateful to Dr Roger W Wiseman for providing the original p53 transgenic mice and Dr Tyler Jacks for providing the original K-ras KO mice. This study was supported in part by NIH Grants R01CA58554 and R01CA78797.

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Authors and Affiliations

  1. Department of Surgery and The Alvin J Siteman Cancer Center, Washington University School of Medicine, St Louis, MI, USA

    Y Wang, Z Zhang & M You

  2. Chemoprevention Branch, National Cancer Institute, Bethesda, MD, USA

    R A Lubet

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  1. Y Wang
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Correspondence to M You.

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Wang, Y., Zhang, Z., Lubet, R. et al. A mouse model for tumor progression of lung cancer in ras and p53 transgenic mice. Oncogene 25, 1277–1280 (2006). https://doi.org/10.1038/sj.onc.1209182

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