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  • Original Paper
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‘Designer’ tumors in mice

Oncogene volume 23, pages 1558–1565 (2004)Cite this article

Abstract

We have developed and tested successfully a general method based on Cre-mediated recombination that can be used for ubiquitous or tissue-specific expression of protein products, including tumor-inducing oncoproteins. Depending on the specificity of a chosen promoter driving cre expression, tumors develop by design in bitransgenic mouse progeny derived by crossing Cre-producing mice with partners carrying a dormant oncogenic transgene (targeted into the 3′ noncoding region of the cytoplasmic β-actin locus) that becomes functional after excision of a ‘floxed’ DNA segment. To provide proof-of-principle, we have used as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T antigens of the SV40 early region (SVER). Cre-dependent activation of widespread SVER expression resulted in hyperplasias or invasive tumors affecting particular visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also encountered spontaneous (Cre-independent) oncogene expression occurring as a rare event, which simulates the initiation of sporadic tumors and leads to PVMT-induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas, thus, revealing particular tissue susceptibilities to the actions of these oncoproteins.

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Acknowledgements

We thank Drs Tom Benjamin, Jean Dahl, Stephen Dilworth and Jim Manley and the laboratory of Dr Michael Getz for kindly providing reagents, Joe Terwilliger, Shouhong Xuan, Zhe Li, and Apostolos Klinakis for discussions, and Elson Ospina, Qiong Li and Lejuan Chatman for expert technical assistance. This work was supported by NCI grants P01 CA75553 (Project 3) and P01 CA97403 (Project 2) to A Efstratiadis. Additional support was provided by grant DAMD17-00-1-0079 from the Department of the Army and by a grant to the Herbert Irving Comprehensive Cancer Center of the Columbia Presbyterian Medical Center from the Avon Products Foundation Breast Cancer Research and Care Program. K Politi was supported by a predoctoral fellowship provided by the Cancer Biology Training Grant T32 CA09503.

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Authors and Affiliations

  1. Department of Genetics and Development, Columbia University, New York, 10032, NY, USA

    Katerina Politi, Ana Kljuic & Argiris Efstratiadis

  2. Department of Pathology, Columbia University, New York, 10032, NY, USA

    Matthias Szabolcs & Peter Fisher

  3. Department of Anatomy and Cell Biology, Columbia University, New York, 10032, NY, USA

    Thomas Ludwig

  4. Institute for Cancer Genetics, Columbia University, New York, 10032, NY, USA

    Thomas Ludwig & Argiris Efstratiadis

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  1. Katerina Politi
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  2. Ana Kljuic
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Correspondence to Argiris Efstratiadis.

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Politi, K., Kljuic, A., Szabolcs, M. et al. ‘Designer’ tumors in mice. Oncogene 23, 1558–1565 (2004). https://doi.org/10.1038/sj.onc.1207275

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