title: Derivation of myoepithelial progenitor cells from bipotent mammary stem/progenitor cells.
abstract: There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Recent molecular profiling has identified six major subtypes of breast cancer: basal-like, ErbB2-overexpressing, normal breast epithelial-like, luminal A and B, and claudin-low subtypes. To help understand the relationship among mammary stem/progenitor cells and breast cancer subtypes, we have recently derived distinct hTERT-immortalized human mammary stem/progenitor cell lines: a K5(+)/K19(-) type, and a K5(+)/K19(+) type. Under specific culture conditions, bipotent K5(+)/K19(-) stem/progenitor cells differentiated into stable clonal populations that were K5(-)/K19(-) and exhibit self-renewal and unipotent myoepithelial differentiation potential in contrast to the parental K5(+)/K19(-) cells which are bipotent. These K5(-)/K19(-) cells function as myoepithelial progenitor cells and constitutively express markers of an epithelial to mesenchymal transition (EMT) and show high invasive and migratory abilities. In addition, these cells express a microarray signature of claudin-low breast cancers. The EMT characteristics of an un-transformed unipotent mammary myoepithelial progenitor cells together with claudin-low signature suggests that the claudin-low breast cancer subtype may arise from myoepithelial lineage committed progenitors. Availability of immortal MPCs should allow a more definitive analysis of their potential to give rise to claudin-low breast cancer subtype and facilitate biological and molecular/biochemical studies of this disease.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhao
authors.forename: Gautam K
authors.initials: GK
authors.lastname: Malhotra
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
authors.forename: Vimla
authors.initials: V
authors.lastname: Band
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D019098:Telomerase
chemical_list: D019098:Telomerase