Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands
Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands
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DOI：
10.1073/pnas.95.2.696
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Dale, E
中科院分区：
文献类型：
--
作者：
Shyamala, G;Yang, X;Dale, E
在这份报告中，我们记录了转基因小鼠的创建，在其中，通过引入额外的A型作为转基因，改变了孕激素受体(PR)的A型和B型的天然比例。我们还表明，在这些小鼠中，乳房发育存在异常。在去卵巢的青春期前PR-A转基因小鼠中，异常形态的末端芽在去卵巢后仍然存在，而在年轻的未去卵巢的小鼠中，乳腺具有广泛的侧向分支，成年小鼠的腺体也表现出导管增生，基底膜紊乱，细胞-细胞黏附减少，这些特征通常与肿瘤有关，因为孕酮是乳腺中的有丝分裂激素，并且PR是乳腺发育所必需的，这些数据提供了直接的证据，表明在体内，这两种PR亚型的调控表达对于细胞对孕酮的适当反应至关重要，并且这对乳腺的发生可能具有重要的意义。
In this report we document the creation of transgenic mice in which the native ratio of A and B forms of progesterone receptor (PR) has been altered by the introduction of additional A form as transgene. We also show that in these mice there is an aberration in mammary development. In ovariectomized prepubertal PR-A transgenic mice, end buds with unusual morphology persist after ovariectomy, and in young adult nonovariectomized mice, mammary glands have extensive lateral branching, The glands of adult mice also exhibit ductal hyperplasia with a disorganized basement membrane and decreased cell-cell adhesion, features commonly associated with neoplasia, Because progesterone is a mitogenic hormone in mammary glands and PR is required for mammary development, these data provide direct evidence that in vivo a regulated expression of the two isoforms of PR is critical for appropriate cellular response to progesterone and that for mammary glands this may have major implications to carcinogenesis.