1. Conditional expression of Ki-RasG12V in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERα)-positive adenocarcinoma
- Author
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D. Rovito, Pietro Rizza, Daniel Metzger, Emprou C, Ines Barone, Stefania Catalano, Gilles Laverny, S. Andò, Salvatore Panza, Rocco Malivindi, Bornert Jm, metzger, daniel, Università della Calabria [Arcavacata di Rende] (Unical), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,mammary gland ,Cancer Research ,medicine.medical_specialty ,Proliferation index ,medicine.drug_class ,[SDV]Life Sciences [q-bio] ,Biology ,Molecular oncology ,Ki-Ras ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Genetics ,medicine ,Molecular Biology ,Cancer ,luminal breast tumors ,medicine.disease ,Antiestrogen ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Endocrinology ,Estrogen ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,carcinogenesis ,Estrogen receptor alpha ,estrogen receptor - Abstract
International audience; 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 to 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 estrogenresponsive, 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, i.e. luminal A subtype, and thus have a high potential for breast cancer research and treatment.
- Published
- 2017
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