Conditional expression of Ki-RasG12V in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERα)-positive adenocarcinoma
Conditional expression of Ki-RasG12V in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERα)-positive adenocarcinoma
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DOI：
10.1038/onc.2017.252
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发表时间：
2017-11-16
期刊：
影响因子：
8
通讯作者：
Metzger, D.
中科院分区：
文献类型：
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作者：
Ando, S.;Malivindi, R.;Metzger, D.
合适的“体内”模型对于研究乳腺癌生物学和评估治疗药物的疗效至关重要。因此，我们设计了一种新型转基因小鼠系，该小鼠系在哺乳后的乳腺上皮中选择性地表达携带激活突变（Ki-Ras（G12 V））的人Ki-Ras。这些小鼠在Ki-Ras（G12 V）诱导后3-9个月内发生侵袭性导管腺癌，发病率为100%。免疫表型分析显示，乳腺肿瘤表达管腔标志物，雌激素和孕激素受体阳性，HER 2阴性，增殖指数低。此外，源自此类肿瘤的细胞系是雌激素响应性的，并且当移植到裸鼠中时，形成对抗雌激素ICI 182780有响应的肿瘤。总之，这些转基因小鼠的乳腺肿瘤和衍生的细胞系表现出人类乳腺癌的主要形式，即管腔A亚型的关键特征，因此具有很高的乳腺癌研究和治疗潜力。
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.