title: A Long-Lived Luminal Subpopulation Enriched with Alveolar Progenitors Serves as Cellular Origin of Heterogeneous Mammary Tumors.
abstract: It has been shown that the mammary luminal lineage could be maintained by luminal stem cells or long-lived progenitors, but their identity and role in breast cancer remain largely elusive. By lineage analysis using Wap-Cre mice, we found that, in nulliparous females, mammary epithelial cells (MECs) genetically marked by Wap-Cre represented a subpopulation of CD61+ luminal progenitors independent of ovarian hormones for their maintenance. Using a pulse-chase lineage-tracing approach based on Wap-Cre adenovirus (Ad-Wap-Cre), we found that Ad-Wap-Cre-marked nulliparous MECs were enriched with CD61+ alveolar progenitors (APs) that gave rise to CD61- alveolar luminal cells during pregnancy/lactation and could maintain themselves long term. When transformed by different oncogenes, they could serve as cells of origin of heterogeneous mammary tumors. Thus, our study revealed a type of long-lived AP within the luminal lineage that may serve as the cellular origin of multiple breast cancer subtypes.
authors.affiliation: Division of Genetics, Brigham and Women's Hospital (BWH), Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Luwei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Division of Genetics, Brigham and Women's Hospital (BWH), Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maaike P A
authors.initials: MP
authors.lastname: van Bragt
authors.affiliation: Division of Genetics, Brigham and Women's Hospital (BWH), Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: zli4@rics.bwh.harvard.edu.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000096:biosynthesis; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D011247:Pregnancy; D013234:Stem Cells / Q000473:pathology
chemical_list: D039661:Integrin beta3