Progesterone action in breast, uterine, and ovarian cancers.
Progesterone action in breast, uterine, and ovarian cancers.
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DOI：
10.1530/jme-14-0252
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发表时间：
2015-04
影响因子：
3.5
通讯作者：
Lange CA
中科院分区：
文献类型：
--
作者：
Diep CH;Daniel AR;Mauro LJ;Knutson TP;Lange CA
孕激素和孕激素受体（PR）对于包括乳腺和生殖道在内的乳腺反应性组织的发育和周期性调节是必不可少的。PR亚型的功能改变有助于这些组织中出现的肿瘤的发病机制。在乳房中，孕酮与雌激素协同作用，促进增殖和促生存基因程序。与此形成鲜明对比的是，孕酮抑制子宫内雌激素驱动的生长，并保护卵巢免于肿瘤转化。不同组织和肿瘤中的孕酮依赖性作用和相关生物学由两种孕酮受体亚型PR-A和PR-B介导。这些异构体受到改变的转录活性或表达水平、与生长因子信号传导途径的差异性串扰以及不同的翻译后修饰和辅因子结合伴侣的影响。在此，我们总结并讨论了最近的文献集中在孕激素和PR亚型的具体行动，在乳腺癌，子宫癌和卵巢癌。了解这些组织中背景依赖性PR作用的复杂性对于开发新模型至关重要，这将使我们能够推进我们的知识基础，目的是揭示这些疾病反应性疾病的新型有效治疗方案。
Progesterone and progesterone receptors (PR) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two progesterone receptor isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential cross-talk with growth factor signaling pathways, and distinct post-translational modifications and cofactor binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases.