Progesterone receptor modulates ERalpha action in breast cancer.

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Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS

Progesterone receptor modulates ERalpha action in breast cancer.

Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8.

PubMed ID

26153859 [ View in PubMed

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Abstract

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

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Progesterone	Estrogen receptor alpha	Protein	Humans	Unknown	Agonist Inhibitor Downregulator	Details