Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease
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Date
2014
Authors
Hilton, H.
Doan, T.
Dinny Graham, J.
Oakes, S.
Silvestri, A.
Santucci, N.
Kantimm, S.
Huschtscha, L.
Ormandy, C.
Funder, J.
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Journal article
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Oncotarget, 2014; 5(18):8651-8664
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Heidi N. Hilton, Tram B. Doan, J. Dinny Graham, Samantha R. Oakes, Audrey Silvestri, Nicole Santucci, Silke Kantimm, Lily I. Huschtscha, Christopher J. Ormandy, John W. Funder, Evan R. Simpson, Elizabeth S. Kuczek, Peter J. Leedman, Wayne D. Tilley, Peter J. Fuller, George E. O. Muscat, and Christine L. Clarke
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Abstract
Cumulative exposure to estrogen (E) and progesterone (P) over the menstrual cycle significantly influences the risk of developing breast cancer. Despite the dogma that PR in the breast merely serves as a marker of an active estrogen receptor (ER), and as an inhibitor of the proliferative actions of E, it is now clear that in the breast P increases proliferation independently of E action. We show here that the progesterone receptor (PR) and ER are expressed in different epithelial populations, and target non-overlapping pathways in the normal human breast. In breast cancer, PR becomes highly correlated with ER, and this convergence is associated with signaling pathways predictive of disease metastasis. These data challenge the established paradigm that ER and PR function co-operatively in normal breast, and have significant implications not only for our understanding of normal breast biology, but also for diagnosis, prognosis and/or treatment options in breast cancer patients.
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© 2014 Hilton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.