Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease

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 Rutherford Simpson, Elizabeth S Kuczek, Peter Jefferey Leedman, Wayne D Tilley, Peter J Fuller, George E O Muscat, Christine L Clarke

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)8651 - 8664
Number of pages14
JournalOncotarget
Volume5
Issue number18
DOIs
Publication statusPublished - 2014

Cite this

Hilton, Heidi N ; Doan, Tram B ; Graham, J Dinny ; Oakes, Samantha R ; Silvestri, Audrey ; Santucci, Nicole ; Kantimm, Silke ; Huschtscha, Lily I ; Ormandy, Christopher J ; Funder, John W ; Simpson, Evan Rutherford ; Kuczek, Elizabeth S ; Leedman, Peter Jefferey ; Tilley, Wayne D ; Fuller, Peter J ; Muscat, George E O ; Clarke, Christine L. / Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease. In: Oncotarget. 2014 ; Vol. 5, No. 18. pp. 8651 - 8664.
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title = "Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease",
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.",
author = "Hilton, {Heidi N} and Doan, {Tram B} and Graham, {J Dinny} and Oakes, {Samantha R} and Audrey Silvestri and Nicole Santucci and Silke Kantimm and Huschtscha, {Lily I} and Ormandy, {Christopher J} and Funder, {John W} and Simpson, {Evan Rutherford} and Kuczek, {Elizabeth S} and Leedman, {Peter Jefferey} and Tilley, {Wayne D} and Fuller, {Peter J} and Muscat, {George E O} and Clarke, {Christine L}",
year = "2014",
doi = "10.18632/oncotarget.2354",
language = "English",
volume = "5",
pages = "8651 -- 8664",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
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Hilton, HN, Doan, TB, Graham, JD, Oakes, SR, Silvestri, A, Santucci, N, Kantimm, S, Huschtscha, LI, Ormandy, CJ, Funder, JW, Simpson, ER, Kuczek, ES, Leedman, PJ, Tilley, WD, Fuller, PJ, Muscat, GEO & Clarke, CL 2014, 'Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease' Oncotarget, vol. 5, no. 18, pp. 8651 - 8664. https://doi.org/10.18632/oncotarget.2354

Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease. / Hilton, Heidi N; Doan, Tram B; Graham, J Dinny; Oakes, Samantha R; Silvestri, Audrey; Santucci, Nicole; Kantimm, Silke; Huschtscha, Lily I; Ormandy, Christopher J; Funder, John W; Simpson, Evan Rutherford; Kuczek, Elizabeth S; Leedman, Peter Jefferey; Tilley, Wayne D; Fuller, Peter J; Muscat, George E O; Clarke, Christine L.

In: Oncotarget, Vol. 5, No. 18, 2014, p. 8651 - 8664.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Acquired convergence of hormone signaling in breast cancer: ER and PR transition from functionally distinct in normal breast to predictors of metastatic disease

AU - Hilton, Heidi N

AU - Doan, Tram B

AU - Graham, J Dinny

AU - Oakes, Samantha R

AU - Silvestri, Audrey

AU - Santucci, Nicole

AU - Kantimm, Silke

AU - Huschtscha, Lily I

AU - Ormandy, Christopher J

AU - Funder, John W

AU - Simpson, Evan Rutherford

AU - Kuczek, Elizabeth S

AU - Leedman, Peter Jefferey

AU - Tilley, Wayne D

AU - Fuller, Peter J

AU - Muscat, George E O

AU - Clarke, Christine L

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226711/pdf/oncotarget-05-8651.pdf

U2 - 10.18632/oncotarget.2354

DO - 10.18632/oncotarget.2354

M3 - Article

VL - 5

SP - 8651

EP - 8664

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 18

ER -