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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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