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  • Original Paper
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Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice

Oncogene volume 21, pages 7831–7838 (2002)Cite this article

Abstract

To investigate the tumorigenic potential of mutant p53 when selectively expressed in lung tissue, a transgenic mouse model was developed in which a mutant form of p53 (p53-273H) was placed under the transcriptional control of the lung-specific human surfactant protein C (SP-C) promoter. Two founder mice were identified, and a line of SP-C/p53-273H transgenic mice was established from one of the founders. Human p53-273H protein was detected specifically in lung tissue from transgenic mice. Malignant tumors, which were histologically characterized as adenocarcinomas, were observed in transgenic mice, with the earliest onset documented at 4 months of age. To further evaluate incidence and onset of tumor formation, transgenic mice (n=113) were sacrificed at age intervals ranging from 4–15 months. At 13–15 months of age, transgenic mice were significantly more likely to have lung tumors at necropsy than age-matched non-transgenic littermates (9 out of 39 (23%) versus 2 out of 35 (5.7%), χ2 test, P=0.036). The SP-C/p53-273H transgenic mice described here thus represent a genetically defined model with which to study the role of p53 mutations in lung tumorigenesis, as well as the potential complementary contributions of other genetic alterations or environmental carcinogens to lung tumor development.

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Acknowledgements

We thank the Transgenic Core Facility of The Ohio State University (OSU), specifically Dr Jan Parker-Thornburg for assistance with the microinjections and Dr Michael Caligiuri for helpful discussions. We also thank the Histology Core Facility at OSU for assistance in histology and immunohistochemistry. The SP-C promoter was kindly supplied by Dr Jeffrey Whitsett (Children's Hospital Medical Center, Cincinnati, OH, USA). The human p53-273H gene was kindly supplied by Dr Arnold J Levine (Rockefeller University). The work was supported by NCI grant K01 CA76970 to MA Villalona-Calero and NCI grant P30 CA16058, to the Ohio State University Comprehensive Cancer Center.

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Authors and Affiliations

  1. Comprehensive Cancer Center, The Ohio State University College of Medicine and Public Health, Columbus, 43210, Ohio, OH, USA

    Wenrui Duan, Haiming Ding, Wei-Guo Zhu, Gary D Stoner, Gregory A Otterson & Miguel A Villalona-Calero

  2. Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Columbus, 43210, Ohio, OH, USA

    Wenrui Duan, Haiming Ding, Wei-Guo Zhu, Gregory A Otterson & Miguel A Villalona-Calero

  3. Department of Public Health, The Ohio State University College of Medicine and Public Health, Columbus, 43210, Ohio, OH, USA

    Gary D Stoner

  4. Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, 43210, Ohio, OH, USA

    Huiming Zhang

  5. Massey Cancer Center and Department of Human Genetics, Virginia Commonwealth University, 23298, Richmond, Virginia, VA, USA

    Mark A Subler & Jolene J Windle

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  1. Wenrui Duan
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Correspondence to Miguel A Villalona-Calero.

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Duan, W., Ding, H., Subler, M. et al. Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice. Oncogene 21, 7831–7838 (2002). https://doi.org/10.1038/sj.onc.1205909

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