title: Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast.
abstract: Progesterone is critical in normal breast development and its synthetic derivatives are emerging as major drivers of breast cancer risk. The recent demonstration that progesterone regulates the stem cell compartment in the murine mammary gland, despite the absence of progesterone receptor (PR) in mammary stem cells, highlights the fact that PR distribution in progenitor cell subsets in the human breast remains to be conclusively shown. By utilising two independent cell sorting strategies to fractionate cells into distinct subpopulations enriched for different cell lineage characteristics, we have demonstrated a consistent enrichment of PR transcripts, relative to estrogen receptor transcripts, in the bipotent progenitor subfraction in the normal human breast. We have also shown co-expression of both steroid hormone receptors with basal markers in a subset of human breast cells, and finally we have demonstrated that PR+ bipotent progenitor cells are estrogen-insensitive, and that estrogen regulates PR in mature luminal cells only.
authors.affiliation: Westmead Institute for Cancer Research, Sydney Medical School-Westmead, University of Sydney at Westmead Millennium Institute, Westmead, New South Wales 2145, Australia. heidi.hilton@sydney.edu.au
authors.forename: H N
authors.initials: HN
authors.lastname: Hilton
authors.forename: J D
authors.initials: JD
authors.lastname: Graham
authors.forename: S
authors.initials: S
authors.lastname: Kantimm
authors.forename: N
authors.initials: N
authors.lastname: Santucci
authors.forename: D
authors.initials: D
authors.lastname: Cloosterman
authors.forename: L I
authors.initials: LI
authors.lastname: Huschtscha
authors.forename: P A
authors.initials: PA
authors.lastname: Mote
authors.forename: C L
authors.initials: CL
authors.lastname: Clarke
mesh_terms: D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001940:Breast / Q000166:cytology* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D053547:Keratin-14 / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D004967:Estrogens; D039503:Integrin alpha6; D053547:Keratin-14; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone