Journal article
Progesterone receptor modulates ERα action in breast cancer
H Mohammed, IA Russell, R Stark, OM Rueda, TE Hickey, GA Tarulli, AAA Serandour, SN Birrell, A Bruna, A Saadi, S Menon, J Hadfield, M Pugh, GV Raj, GD Brown, C D'Santos, JLL Robinson, G Silva, R Launchbury, CM Perou Show all
Nature | NATURE PORTFOLIO | Published : 2015
DOI: 10.1038/nature14583
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 o..
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Awarded by National Institutes of Health
Funding 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. Research reported in this manuscript was supported by the National Cancer Institute of 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.