Progesterone receptor modulates ER? action in breast cancer.

ABSTRACT: Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-? (ER?) function and breast cancer prognosis. Here we show that PR is not merely an ER?-induced gene target, but is also an ER?-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ER? to direct ER? 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 ER?(+) cell line xenografts and primary ER?(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ER? antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ER?(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ER? chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

SUBMITTER: Mohammed H 

PROVIDER: S-EPMC4650274 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature