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.
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Heidi N
authors.initials: HN
authors.lastname: Hilton
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Tram B
authors.initials: TB
authors.lastname: Doan
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: J Dinny
authors.initials: JD
authors.lastname: Graham
authors.affiliation: Cancer Research Program and The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. St Vincent's Clinical School, St Vincent's Hospital and University of New South Wales, Darlinghurst NSW, Australia.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Oakes
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Audrey
authors.initials: A
authors.lastname: Silvestri
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Santucci
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Silke
authors.initials: S
authors.lastname: Kantimm
authors.affiliation: Children's Medical Research Institute, Westmead, New South Wales, Australia.
authors.forename: Lily I
authors.initials: LI
authors.lastname: Huschtscha
authors.affiliation: Cancer Research Program and The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia. St Vincent's Clinical School, St Vincent's Hospital and University of New South Wales, Darlinghurst NSW, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
authors.affiliation: MIMR-PHI Institute, Clayton, Victoria, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Funder
authors.affiliation: MIMR-PHI Institute, Clayton, Victoria, Australia.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.affiliation: Sydney Medical School, University of Sydney, Westmead, NSW, Australia.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Kuczek
authors.affiliation: Laboratory for Cancer Medicine, Centre for Medical Research, Western Australian Institute for Medical Research and School of Medicine and Pharmacology, the University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
authors.affiliation: Dame Roma Mitchell Cancer Research Laboratories, Discipline of Medicine, Hanson Institute, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
authors.affiliation: MIMR-PHI Institute, Clayton, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: George E O
authors.initials: GE
authors.lastname: Muscat
authors.affiliation: Westmead Millennium Institute, Sydney Medical School - Westmead, University of Sydney, NSW, Australia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Clarke
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D019070:Cell Lineage; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D053208:Kaplan-Meier Estimate; D008321:Mammary Glands, Animal / Q000378:metabolism*; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020239:Receptor Cross-Talk; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone