title: Defining the cellular precursors to human breast cancer.
abstract: Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM(+)) and basal/myoepithelial (CD10(+)). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM(+) epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10(+) cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10(+) breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.
authors.affiliation: Department of Anatomy and Cellular Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Keller
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Arendt
authors.forename: Adam
authors.initials: A
authors.lastname: Skibinski
authors.forename: Tanya
authors.initials: T
authors.lastname: Logvinenko
authors.forename: Ina
authors.initials: I
authors.lastname: Klebba
authors.forename: Shumin
authors.initials: S
authors.lastname: Dong
authors.forename: Avi E
authors.initials: AE
authors.lastname: Smith
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Hannah
authors.initials: H
authors.lastname: Gilmore
authors.forename: Stuart
authors.initials: S
authors.lastname: Schnitt
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Naber
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Garlick
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008679:Metaplasia; D015260:Neprilysin / Q000378:metabolism; D010641:Phenotype
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D015260:Neprilysin