黃體酮(孕酮)和它們的受體(PR)以及雌激素和它們的受體 (ERα和ERβ)在正常乳房發(fā)育和體內(nèi)平衡中以及在乳腺癌中都發(fā)揮關(guān)鍵作用。在乳腺癌中，這些受體的存在已被用作乳腺癌是否會對ER受體拮抗劑有反應(yīng)的一個預(yù)后標(biāo)志。它們功能之間的關(guān)系此前還不是完全清楚，現(xiàn)在Jason Carroll及同事通過顯示PR控制ERα功能揭示了這個謎底的一個關(guān)鍵構(gòu)成部分。 通過重新引導(dǎo)ERα與染色質(zhì)的結(jié)合位置，它在ERα+ 乳腺癌中充當(dāng)控制增生的一個“剎車”裝置。相應(yīng)地，PGR基因(該基因編碼PR)的喪失與乳腺癌患者預(yù)后較差相關(guān)。

原文內(nèi)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.

原文鏈接：http://www.nature.com/nature/journal/v523/n7560/full/nature14583.html