Progesterone receptors in mammary gland development and tumorigenesis
Progesterone receptors in mammary gland development and tumorigenesis
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DOI：
10.1023/a:1025952924864
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发表时间：
2003-04-01
影响因子：
2.5
通讯作者：
Lydon, JP
中科院分区：
文献类型：
--
作者：
Conneely, OM;Jericevic, BM;Lydon, JP
类固醇激素孕酮（P）是女性生殖活动各个方面的中心协调者，在妊娠相关乳腺形态发生和乳腺肿瘤发生中起关键作用。P对乳腺的作用是由两种结构和功能不同的核受体PR-A和PR-B介导的，这两种受体来自一个基因。PR基因敲除（PRKO）小鼠中两种受体的突变已证明PR在介导妊娠相关的乳腺导管分支和小叶肺泡分化以及在响应致癌物的乳腺肿瘤的起始中起关键作用。最近，对PRKO小鼠中被破坏的分子遗传途径的分析产生了对PR调节乳腺形态发生的分子机制的重要见解。除了其在调节妊娠期间成年乳腺的增殖和分化反应中的重要作用外，P在早期奇偶校验提供的对乳腺肿瘤发生的保护中起着关键作用。因此，P对出生后发育可塑性的乳腺不同的年轻和成年腺体之间的影响。本文综述了近年来在以下方面的研究进展：1）孕激素受体介导妊娠相关乳腺形态发生的分子机制; 2）孕激素受体在成年乳腺对致癌物的致瘤反应中的作用; 3）孕激素受体在幼年乳腺长期保护中的作用。此外，我们将总结最近的见解的亚型选择性贡献的一些这些活动的PR获得的比较分析P-依赖性乳腺发育的PR亚型特异性基因敲除小鼠缺乏PR-A（PRAKO）或PR-B（PRBKO）。
The steroid hormone, progesterone (P), is a central coordinator of all aspects of female reproductive activity and plays a key role in pregnancy-associated mammary gland morphogenesis and mammary tumorigenesis. The effects of P on the mammary gland are mediated by two structurally and functionally distinct nuclear receptors PR-A and PR-B that arise from a single gene. Null mutation of both receptors in PR knockout (PRKO) mice has demonstrated a critical role for PRs in mediating pregnancy-associated mammary ductal branching and lobuloalveolar differentiation and in initiation of mammary tumors in response to carcinogen. Analysis of the molecular genetic pathways disrupted in PRKO mice has recently yielded important insights into the molecular mechanisms of regulation of mammary gland morphogenesis by PRs. In addition to its essential role in regulating proliferative and differentiative responses of the adult mammary gland during pregnancy, P plays a critical role in the protection against mammary tumorigenesis afforded by early parity. Thus, the effects of P on postnatal developmental plasticity of the mammary gland differ between young and adult glands. This review will summarize recent advances in our understanding of 1) the molecular mechanisms by which PRs mediate pregnancy-associated mammary gland morphogenesis, 2) the role of PRs in mediating tumorigenic responses of the adult mammary gland to carcinogen, and 3) the role of P in long-term protection of the juvenile mammary gland against tumorigenesis. In addition, we will summarize recent insights into the isoform selective contributions to some of these activities of PRs obtained from comparative analysis of P-dependent mammary gland development in PR isoform specific knockout mice lacking either the PR-A (PRAKO) or PR-B (PRBKO).