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Keywords {🔍}

cells, cell, mammary, luminal, breast, pubmed, aldh, human, article, expression, cancer, mouse, populations, google, scholar, progenitors, additional, figure, file, cas, epithelial, population, basal, stem, mice, erbb, progenitor, gland, subpopulations, gene, results, levels, distribution, differentiation, normal, types, central, analysis, oestrogen, tumours, research, lps, cambridge, krt, potential, receptor, ncl, epithelium, observed, outgrowths,

Topics {✒️}

chamber poly-lysine-coated slides double-sorted oestrogen receptor-negative quantitative rt-pcr confirms article download pdf quantitative rt-pcr analysis kluwer academic/plenum press real-time pcr reactions li ka-shing centre total colony-forming cell carlos caldas female nod/scid il2rγc-/ dimensional colony-forming cell milk-producing alveolar cell node-negative breast cancer asselin-labat ml erbb2-induced mammary tumorigenesis fluorescence-activated cell sorting cell-type-specific centroids growth factor-reduced matrigel related subjects delta-delta method normalised anti-rabbit antibody conjugated cell-type-specific signatures er+ progenitor-specific promoter c-kit antibody clone nonclonogenic oestrogen receptor-positive alveolar cell fate post-involution mammary cells basally-positioned myoepithelial cells estrogen receptor-positive cells low oestrogen/progesterone environment flow-sorted mouse cells double-sorted er- progenitors c-kit expression identifies examining c-kit expression cd24highsca1-c-kit+ phenotype illumina bead-based data mammary repopulating unit primitive progenitor cell flow-sorted luminal cells establish parent-progeny relationships epcam+cd44+cd24-/low phenotype [34] mammary epithelial hierarchy luminal-restricted progenitor population false discovery rate rnase-free dnase set single stem cell breast cell type c-kit expression levels breast cancer profiles

Questions {❓}

• Gusterson B: Do 'basal-like' breast cancers really exist?

Schema {🗺️}

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         headline:Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland
         description:The organisation of the mammary epithelial hierarchy is poorly understood. Our hypothesis is that the luminal cell compartment is more complex than initially described, and that an understanding of the developmental relationships within this lineage will help in understanding the cellular context in which breast tumours occur. We used fluorescence-activated cell sorting along with in vitro and in vivo functional assays to examine the growth and differentiation properties of distinct subsets of human and mouse mammary epithelial cells. We also examined how loss of steroid hormones influenced these populations in vivo. Gene expression profiles were also obtained for all the purified cell populations and correlated to those obtained from breast tumours. The luminal cell compartment of the mouse mammary gland can be resolved into nonclonogenic oestrogen receptor-positive (ER+) luminal cells, ER+ luminal progenitors and oestrogen receptor-negative (ER-) luminal progenitors. The ER+ luminal progenitors are unique in regard to cell survival, as they are relatively insensitive to loss of oestrogen and progesterone when compared with the other types of mammary epithelial cells. Analysis of normal human breast tissue reveals a similar hierarchical organisation composed of nonclonogenic luminal cells, and relatively differentiated (EpCAM+CD49f+ALDH-) and undifferentiated (EpCAM+CD49f+ALDH+) luminal progenitors. In addition, approximately one-quarter of human breast samples examined contained an additional population that had a distinct luminal progenitor phenotype, characterised by low expression of ERBB3 and low proliferative potential. Parent-progeny relationship experiments demonstrated that all luminal progenitor populations in both species are highly plastic and, at low frequencies, can generate progeny representing all mammary cell types. The ER- luminal progenitors in the mouse and the ALDH+ luminal progenitors in the human appear to be analogous populations since they both have gene signatures that are associated with alveolar differentiation and resemble those obtained from basal-like breast tumours. The luminal cell compartment in the mammary epithelium is more heterogeneous than initially perceived since progenitors of varying levels of luminal cell differentiation and proliferative capacities can be identified. An understanding of these cells will be essential for understanding the origins and the cellular context of human breast tumours.
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            Luminal Progenitor
            Express Oestrogen Receptor
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland
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         Luminal Cell
         Mouse Mammary Gland
         Mouse Mammary Epithelial Cell
         Luminal Progenitor
         Express Oestrogen Receptor
         Cancer Research
         Oncology
         Surgical Oncology
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               type:PostalAddress
            type:Organization
            name:Breast Cancer Functional Genomics Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre
            address:
               name:Breast Cancer Functional Genomics Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:Christine J Watson
      affiliation:
            name:University of Cambridge
            address:
               name:Department of Pathology, University of Cambridge, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:John Stingl
      affiliation:
            name:Cambridge Research Institute, Li Ka-Shing Centre
            address:
               name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Statistical Cancer Genomics, UCL Cancer Institute, University College London, London, UK
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Department of Pathology, Technical University Munich, Munich, Germany
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, Canada
      name:Department of Oncology, University of Cambridge, Worts Causeway, UK
      name:Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital NHS, Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, UK
      name:Cambridge Experimental Cancer Medicine Centre, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Breast Cancer Functional Genomics Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK
      name:Department of Pathology, University of Cambridge, Cambridge, UK
      name:Mammary Stem Cell Laboratory, Cancer Research UK, Cambridge Research Institute, Li Ka-Shing Centre, Cambridge, UK

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