2.50
Hdl Handle:
http://hdl.handle.net/10541/76276
Title:
Isolation and characterization of human mammary stem cells.
Authors:
Clarke, Robert B
Abstract:
Since 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.
Affiliation:
Breast Biology Group, Division of Cancer Studies, University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK. robert.clarke@manchester.ac.uk
Citation:
Isolation and characterization of human mammary stem cells. 2005, 38 (6):375-86 Cell Prolif.
Journal:
Cell Proliferation
Issue Date:
Dec-2005
URI:
http://hdl.handle.net/10541/76276
DOI:
10.1111/j.1365-2184.2005.00357.x
PubMed ID:
16300651
Type:
Article
Language:
en
ISSN:
0960-7722
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorClarke, Robert B-
dc.date.accessioned2009-08-04T17:14:09Z-
dc.date.available2009-08-04T17:14:09Z-
dc.date.issued2005-12-
dc.identifier.citationIsolation and characterization of human mammary stem cells. 2005, 38 (6):375-86 Cell Prolif.en
dc.identifier.issn0960-7722-
dc.identifier.pmid16300651-
dc.identifier.doi10.1111/j.1365-2184.2005.00357.x-
dc.identifier.urihttp://hdl.handle.net/10541/76276-
dc.description.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.en
dc.language.isoenen
dc.subject.meshBreast-
dc.subject.meshCell Separation-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshStem Cells-
dc.titleIsolation and characterization of human mammary stem cells.en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, Division of Cancer Studies, University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK. robert.clarke@manchester.ac.uken
dc.identifier.journalCell Proliferationen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.