Introduction of estrogen receptor-α into the tTA/TAg conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma
Introduction of estrogen receptor-α into the tTA/TAg conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma
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DOI：
10.1016/s0002-9440(10)63529-8
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发表时间：
2003-11-01
影响因子：
6
通讯作者：
Furth, PA
中科院分区：
文献类型：
--
作者：
Tilli, MT;Frech, MS;Furth, PA
将雌激素受体(ER)-α的条件性表达引入四环素反应性MMTV-TTA/TETOP-Tag小鼠，建立雌激素反应性ER-α阳性乳腺癌小鼠模型。小鼠发生乳腺腺癌，平均潜伏期为11个月。早期病变包括导管增生和增生性肺泡结节，在4个月大时出现。乳腺癌表现出与人类乳腺癌相似的组织学特征。对腺癌裂解物进行的ER类固醇结合研究表明，它与雌二醇结合。在去卵巢裸鼠体内进行的有无雌二醇的肿瘤组织块研究表明，雌激素刺激了乳腺肿瘤的生长。此外，ER-α的存在改变了TTA/TAG雌性小鼠中其他MMTV靶向组织中的肿瘤光谱。淋巴瘤发生在40%的Tta/Tag雌性小鼠中，仅在4%的Tta/Tag/ER-α小鼠中发现(P=0.014，卡方检验)。这些实验证明，以乳腺上皮细胞为靶点的ER-α转基因可用于建立ER-α反应性乳腺癌的小鼠模型。
Conditional expression of estrogen receptor (ER)-alpha was introduced into tetracycline-responsive MMTV-tTA/tetop-TAg mice to develop a mouse model of estrogen-responsive ER-alpha-positive mammary adenocarcinoma. Mammary adenocarcinomas developed in the mice with a mean latency of 11 months. Precursor lesions including ductal hyperplasia and hyperplastic alveolar nodules were present by the age of 4 months. The mammary adenocarcinomas exhibited histological features similar to human breast cancers. ER steroid-binding studies conducted on adenocarcinoma lysates demonstrated binding to estradiol. Tumor explant studies in the presence and absence of estradiol in ovariectomized athymic nude mice revealed that growth of mammary tumors was stimulated by estrogen. In addition, the presence of ER-alpha altered the tumor spectrum in other MMTV-targeted tissues in the tTA/TAg female mice. Lymphomas, which develop in 40% of tTA/TAg female mice, were found in only 4% of tTA/TAg/ER-alpha mice (P = 0.014, chi-square test). These experiments demonstrate that the introduction of an ER-alpha transgene targeted to mammary epithelial cells can be used to develop mouse models of ER-alpha-responsive mammary cancer.