文章：

孕激素在乳腺癌中的信号：一种被忽视的激素成为人们关注的焦点

Progesterone signalling in breast cancer: a neglected hormone coming into the limelight

原文发布日期：2013-05-24

DOI: 10.1038/nrc3518

类型: Review Article

开放获取: 否

要点：

1. Mutations are not always sufficient to drive breast carcinogenesis but additional factors determine whether genetically altered cells progress to the state during which they provoke clinically manifest disease.
2. The ovarian steroid hormones, 17β-oestradiol and progesterone, are pivotal in the control of breast development and physiology and are intimately linked to mammary carcinogenesis. Their respective roles in vivo have begun to be dissected in the mouse model.
3. 17β-oestradiol and progesterone act on a subset of cells that express the respective receptors and elicit paracrine signalling.
4. Progesterone has emerged as the major mitogen in the adult mammary epithelium in both mice and humans.
5. The major proliferative control axis progesterone–receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) is conserved between mice and humans.
6. Interfering with progesterone receptor (PR) signalling and paracrine signalling holds promise for breast cancer prevention and therapy.

要点翻译：

1. 突变并不总是足以驱动乳腺癌的发生，而是需要其他因素来决定遗传改变的细胞是否进展到引发临床显性疾病的阶段。
2. 卵巢类固醇激素——17β-雌二醇和孕酮，在调控乳房发育和生理过程中至关重要，并且与乳腺致癌机制密切相关。它们在小鼠模型中的体内作用已开始被解析。
3. 17β-雌二醇和孕酮作用于表达相应受体的细胞亚群，并引发旁分泌信号传导。
4. 在成年小鼠和人类的乳腺上皮中，孕酮已成为主要的促有丝分裂原。
5. 孕酮-核因子κB（NF-κB）受体激活剂配体（RANKL）这一主要增殖调控轴在小鼠和人类之间是保守的。
6. 干扰孕酮受体（PR）信号传导及旁分泌信号传导为乳腺癌的预防和治疗带来了希望。

英文摘要：

Understanding the biology of the breast and how ovarian hormones impinge on it is key to rational new approaches in breast cancer prevention and therapy. Because of the success of selective oestrogen receptor modulators (SERMs), such as tamoxifen, and aromatase inhibitors in breast cancer treatment, oestrogens have long received the most attention. Early progesterone receptor (PR) antagonists, however, were dismissed because of severe side effects, but awareness is now increasing that progesterone is an important hormone in breast cancer. Oestrogen receptor-α (ERα) signalling and PR signalling have distinct roles in normal mammary gland biology in mice; both ERα and PR delegate many of their biological functions to distinct paracrine mediators. If the findings in the mouse model translate to humans, new preventive and therapeutic perspectives might open up.

摘要翻译： 

理解乳腺的生物学以及卵巢激素如何影响它是乳腺癌预防和治疗新方法的关键。由于选择性雌激素受体调节剂（SERMs）如他莫昔芬以及芳香化酶抑制剂在乳腺癌治疗中的成功，雌激素长期以来受到了最多的关注。然而，早期的孕激素受体（PR）拮抗剂因严重的副作用而被忽视，但现在人们越来越意识到孕激素是乳腺癌中的一个重要激素。在小鼠的正常乳腺腺生物学中，雌激素受体-α（ERα）信号传导和PR信号传导有着不同的角色；ERα和PR都将它们的许多生物学功能委托给不同的旁分泌介质。如果小鼠模型中的发现能够转化为人类，可能会开启新的预防和治疗的视角。

原文链接：

Progesterone signalling in breast cancer: a neglected hormone coming into the limelight