title: Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue.
abstract: The purpose of the present study was to characterize primitive epithelial progenitor populations present in adult normal human mammary tissue using a combination of flow cytometry and in vitro colony assay procedures. Three types of human breast epithelial cell (HBEC) progenitors were identified: luminal-restricted, myoepithelial-restricted and bipotent progenitors. The first type expressed epithelial cell adhesion molecule (EpCAM), alpha6 integrin and MUC1 and generated colonies composed exclusively of cells positive for the luminal-associated markers keratin 8/18, keratin 19, EpCAM and MUC1. Bipotent progenitors produced colonies containing a central core of cells expressing luminal markers surrounded by keratin 14+ myoepithelial-like cells. Single cell cultures confirmed the bipotentiality of these progenitors. Their high expression of alpha6 integrin and low expression of MUC1 suggests a basal position of these cells in the mammary epithelium in vivo. Serial passage in vitro of an enriched population of bipotent progenitors demonstrated that only myoepithelial-restricted progenitors could be readily generated under the culture conditions used. These results support a hierarchical branching model of HBEC progenitor differentiation from a primitive uncommitted cell to luminal- and myoepithelial-restricted progenitors.
authors.affiliation: Department of Anatomy, University of British Columbia, Vancouver, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Stingl
authors.forename: C J
authors.initials: CJ
authors.lastname: Eaves
authors.forename: I
authors.initials: I
authors.lastname: Zandieh
authors.forename: J T
authors.initials: JT
authors.lastname: Emerman
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis; D001940:Breast / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000096:biosynthesis; D018396:Mucin-1 / Q000096:biosynthesis; D013234:Stem Cells / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D016023:Integrins; D018396:Mucin-1