title: Progesterone stimulates progenitor cells in normal human breast and breast cancer cells.
abstract: The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. We previously demonstrated that P treatment increases proliferation and augments the number of progenitor-like cells, and that the progesterone receptor (PR) is also expressed in the bipotent progenitor-enriched subfraction. Here we demonstrate that PR is expressed in a subset of CD10+ basal cells and that P stimulates this CD10+ cell compartment, which is enriched for bipotent progenitor activity. In addition, we have shown that P stimulates progenitor cells in human breast cancer cell lines and expands the cancer stem cell population via increasing the stem-like CD44+ population. As changes in cell type composition are one of the hallmark features of breast cancer progression, the demonstration that progenitor cells are stimulated by P in both normal breast and in breast cancer cells has critical implications in discerning the mechanisms of how P increases breast cancer risk.
authors.affiliation: Westmead Institute for Cancer Research, Sydney Medical School, University of Sydney at Westmead Millennium Institute, Westmead, NSW, 2145, Australia, heidi.hilton@sydney.edu.au.
authors.forename: Heidi N
authors.initials: HN
authors.lastname: Hilton
authors.forename: N
authors.initials: N
authors.lastname: Santucci
authors.forename: A
authors.initials: A
authors.lastname: Silvestri
authors.forename: S
authors.initials: S
authors.lastname: Kantimm
authors.forename: L I
authors.initials: LI
authors.lastname: Huschtscha
authors.forename: J D
authors.initials: JD
authors.lastname: Graham
authors.forename: C L
authors.initials: CL
authors.lastname: Clarke
mesh_terms: D001940:Breast / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects; D015260:Neprilysin / Q000235:genetics; D011374:Progesterone / Q000008:administration & dosage* / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects
chemical_list: D018960:Hyaluronan Receptors; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol; D015260:Neprilysin