黄体酮(孕酮)和它们的受体(PR)以及雌激素和它们的受体 (ERα和ERβ)在正常乳房发育和体内平衡中以及在乳腺癌中都发挥关键作用。在乳腺癌中，这些受体的存在已被用作乳腺癌是否会对ER受体拮抗剂有反应的一个预后标志。它们功能之间的关系此前还不是完全清楚，现在Jason Carroll及同事通过显示PR控制ERα功能揭示了这个谜底的一个关键构成部分。 通过重新引导ERα与染色质的结合位置，它在ERα+ 乳腺癌中充当控制增生的一个“刹车”装置。相应地，PGR基因(该基因编码PR)的丧失与乳腺癌患者预后较差相关。
原文内容：Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-α (ERα) function and breast cancer prognosis. Here we show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumour explants, and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERα+ breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.
原文链接：http://www.nature.com/nature/journal/v523/n7560/full/nature14583.html