Progesterone receptor modulates ERalpha action in breast cancer
Menée à l'aide de xénogreffes de cancer du sein, cette étude met en évidence des mécanismes par lesquels le récepteur de la progestérone régule l'activité du récepteur alpha des estrogènes
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.