@article{2a144ebef9d74aedaaf4a913ac47031b,
title = "Progesterone receptor modulates ERα action in breast cancer",
abstract = "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.",
author = "Hisham Mohammed and Russell, {I. Alasdair} and Rory Stark and Rueda, {Oscar M.} and Hickey, {Theresa E.} and Tarulli, {Gerard A.} and Serandour, {Aurelien A A} and Birrell, {Stephen N.} and Alejandra Bruna and Amel Saadi and Suraj Menon and James Hadfield and Michelle Pugh and Raj, {Ganesh V.} and Brown, {Gordon D.} and Clive D'Santos and Robinson, {Jessica L L} and Grace Silva and Rosalind Launchbury and Perou, {Charles M.} and John Stingl and Carlos Caldas and Tilley, {Wayne D.} and Carroll, {Jason S.}",
note = "Funding Information: Acknowledgements The authors would like to thank S. Leigh-Brown, the staff in the genomic core facility, S. Halim, the proteomic core facility and the bioinformatic core facility at Cancer Research UK. We acknowledge S. Jindal for pathology review, N. Ryan for technical assistance and S. Edwards for statistical analysis with ex vivo culture. The MCF7-LucYFP cells were a kind gift from N. Benaich. We thank H. Gronemeyer for the PR-A and PR-B expressing vectors. We would like to acknowledge the support of the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. Researchreported inthismanuscriptwas supported bytheNationalCancerInstituteof the National Institutes of Health under award number 5P30CA142543 (to University of Texas Southwestern) and Department of Defense grants W81XWH-12-1-0288-03 (GVR). W.D.T. is supported by grants from the National Health and Medical Research Council of Australia (ID 1008349; ID 1084416) and Cancer Australia (ID 627229) T.E.H. held a Fellowship Award from the US Department of Defense Breast Cancer Research Program (BCRP; W81XWH-11-1-0592) and currently is supported by a Florey Fellowship from the Royal Adelaide Hospital Research Foundation. J.S.C. is supported by an ERC starting grant and an EMBO Young investigator award. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jul,
day = "16",
doi = "10.1038/nature14583",
language = "English (US)",
volume = "523",
pages = "313--317",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7560",
}