Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/93423
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Type: Journal article
Title: Progesterone receptor modulates ERα action in breast cancer
Other Titles: Progesterone receptor modulates ERalpha action in breast cancer
Author: Mohammed, H.
Russell, I.
Stark, R.
Rueda, O.
Hickey, T.
Tarulli, G.
Serandour, A.
Birrell, S.
Bruna, A.
Saadi, A.
Menon, S.
Hadfield, J.
Pugh, M.
Raj, G.
Brown, G.
D'Santos, C.
Robinson, J.
Silva, G.
Launchbury, R.
Perou, C.
et al.
Citation: Nature, 2015; 523(7560):313-317
Publisher: NATURE PORTFOLIO
Issue Date: 2015
ISSN: 0028-0836
1476-4687
Statement of
Responsibility: 
Hisham Mohammed, I. Alasdair Russell, Rory Stark, Oscar M. Rueda, Theresa E. Hickey, Gerard A. Tarulli, Aurelien A. Serandour, Stephen N. Birrell, Alejandra Bruna, Amel Saadi, Suraj Menon, James Hadfield, Michelle Pugh, Ganesh V. Raj, Gordon D. Brown, Clive D, Santos, Jessica L. L. Robinson, Grace Silva, Rosalind Launchbury, Charles M. Perou, John Stingl, Carlos Caldas, Wayne D. Tilley, Jason S. Carroll
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.
Keywords: Cell Line, Tumor
Chromatin
Animals
Humans
Mice
Breast Neoplasms
Disease Progression
Progesterone
Estrogen Receptor alpha
Receptors, Progesterone
Estrogens
Ligands
Xenograft Model Antitumor Assays
Cell Proliferation
Transcription, Genetic
Gene Expression Regulation, Neoplastic
Protein Binding
Female
DNA Copy Number Variations
Description: Corrigendum: 10.1038/nature14959 In this Article, author Aurelien A. Serandour should have been listed with one middle initial only. This has been corrected in the online versions.
Rights: © 2015 Macmillan Publishers Limited. All rights reserved.
DOI: 10.1038/nature14583
Grant ID: http://purl.org/au-research/grants/nhmrc/1008349
http://purl.org/au-research/grants/nhmrc/1084416
Published version: http://dx.doi.org/10.1038/nature14583
Appears in Collections:Aurora harvest 2
Medicine publications

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