AuthorsClarke, Robert B
AffiliationBreast Biology Group, Division of Cancer Studies, University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK. email@example.com
MetadataShow full item record
AbstractSince stem cells are present throughout the lifetime of an organism, it is thought that they may accumulate mutations, eventually leading to cancer. In the breast, tumours are predominantly oestrogen and progesterone receptor-positive (ERalpha/PR+). We therefore studied the biology of ERalpha/PR-positive cells and their relationship to stem cells in normal human mammary epithelium. We demonstrated that ERalpha/PR-positive cells co-express the putative stem cell markers p21(CIP1/WAF1), cytokeratin (CK) 19 and Musashi-1 when examined using dual label immunofluorescence on tissue sections. Next, we isolated a Hoechst dye-effluxing 'side population' (SP) from the epithelium using flow cytometry and demonstrated them to be undifferentiated cells by lack of expression of myoepithelial and luminal cell-specific antigens such as CALLA and MUC1. Epithelial SP cells were shown to be enriched for the putative stem cell markers p21(CIP1/WAF1), Musashi-1 and ERalpha/PR-positive cells. Lastly, SP cells, compared to non-SP, were highly enriched for the capacity to produce colonies containing multiple lineages in 3D basement membrane (Matrigel) culture. We conclude that breast stem cells include two populations: a primitive ERalpha/PR-negative stem cell necessary for development and a shorter term ERalpha/PR-positive stem cell necessary for adult tissue homeostasis during menstrual cycling. We speculate these two basic stem cell types may therefore be the cells of origin for ERalpha-positive and -negative breast tumours.
CitationIsolation and characterization of human mammary stem cells. 2005, 38 (6):375-86 Cell Prolif.
- Regulation of human breast epithelial stem cells.
- Authors: Clarke RB, Anderson E, Howell A, Potten CS
- Issue date: 2003 Oct
- A putative human breast stem cell population is enriched for steroid receptor-positive cells.
- Authors: Clarke RB, Spence K, Anderson E, Howell A, Okano H, Potten CS
- Issue date: 2005 Jan 15
- Growth and differentiation of progenitor/stem cells derived from the human mammary gland.
- Authors: Clayton H, Titley I, Vivanco Md
- Issue date: 2004 Jul 15
- Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast.
- Authors: Stingl J, Eaves CJ, Kuusk U, Emerman JT
- Issue date: 1998 Aug
- Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity.
- Authors: Chamberlin T, D'Amato JV, Arendt LM
- Issue date: 2017 Nov 29