Abstract
Appropriate ‘in vivo’ models are crucial for studying breast cancer biology and evaluating the efficacy of therapeutic agents. Thus we engineered a novel transgenic mouse line expressing the human Ki-Ras bearing an activating mutation (Ki-Ras(G12V)) selectively in the mammary epithelium after lactation. These mice develop invasive ductal adenocarcinomas with 100% incidence within 3–9 months after Ki-Ras(G12V) induction. Immunophenotyping revealed that the mammary tumors express luminal markers, are positive for estrogen and progesterone receptors, negative for HER2 and have a low proliferation index. Moreover, cell lines derived from such tumors are estrogen-responsive and, when transplanted into nude mice, form tumors that respond to the antiestrogen ICI 182780. In conclusion, the mammary tumors of these transgenic mice and the derived cell lines exhibit key features of the major form of human breast cancer, that is, luminal A subtype and thus have a high potential for breast cancer research and treatment.
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Acknowledgements
We thank Dr Watson and Dr Whitelaw for BLG-Cre mice, Merck Research Laboratories for the MMTV-Ki-Ras(G12V) plasmid and Catherine Tomasetto and Fabien Alpy for helpful discussions. We also thank Neil E Hubbard and Judith Walls (Center for Comparative Medicine, University of California, Davis, CA, USA), the staff of the mouse and genetic engineering facilities from ICS and IGBMC and Elise Grelet for their excellent assistance. This work was supported by: PRIN2015 #2015B7M39T (to SA), Fondazione Italiana per la Ricerca sul Cancro (AIRC) grants: IG no. 11595 (to SA), MFAG no. 16899 (to IB), PROGRAMMA ‘FUTURO IN RICERCA’ Anno 2012 no. RBFR12FI27 (to IB), AIRC Fellowships for abroad no. 19552 (to DR), EMBO ASTF no. 18-2010 (to RM), European Social Fund operational programme of the Calabria region (to SP), Faculté de Médecine, Université de Strasbourg (to CE) and by the Centre National pour la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM), the Université de Strasbourg and French state funds through the Agence Nationale de la Recherche ANR-10-LABX-0030-INRT under the frame programme Investissements d’Avenir labelled ANR-10-IDEX-0002-02.
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Andò, S., Malivindi, R., Catalano, S. et al. Conditional expression of Ki-RasG12V in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERα)-positive adenocarcinoma. Oncogene 36, 6420–6431 (2017). https://doi.org/10.1038/onc.2017.252
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DOI: https://doi.org/10.1038/onc.2017.252
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