Conditional expression of Ki-Ras G12V in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERα)-positive adenocarcinoma

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 ) selectively in the mammary epithelium after l...

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Bibliographic Details
Published in:Oncogene 2017-11, Vol.36 (46), p.6420
Main Authors: Andò, S, Malivindi, R, Catalano, S, Rizza, P, Barone, I, Panza, S, Rovito, D, Emprou, C, Bornert, J-M, Laverny, G, Metzger, D
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Animals
Epithelium - metabolism
Estradiol - analogs & derivatives
Estradiol - pharmacology
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen Receptor Antagonists - pharmacology
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Genes, ras - genetics
Humans
Mammary Glands, Animal - metabolism
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - metabolism
MCF-7 Cells
Mice, Inbred C57BL
Mice, Nude
Mice, Transgenic
Mutation, Missense
Tumor Cells, Cultured
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Summary: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 ) selectively in the mammary epithelium after lactation. These mice develop invasive ductal adenocarcinomas with 100% incidence within 3-9 months after Ki-Ras 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.
ISSN:1476-5594