A putative human breast stem cell population is enriched for steroid receptor-positive cells.

2.50
Hdl Handle:
http://hdl.handle.net/10541/75866
Title:
A putative human breast stem cell population is enriched for steroid receptor-positive cells.
Authors:
Clarke, Robert B; Spence, Katherine; Anderson, Elizabeth; Howell, Anthony ( 0000-0002-3879-5991 ) ; Okano, Hideyuki; Potten, Christopher S
Abstract:
Breast epithelial stem cells are thought to be the primary targets in the etiology of breast cancer. Since breast cancers mostly express estrogen and progesterone receptor (ERalpha and PR), we examined the biology of these ERalpha/PR-positive cells and their relationship to stem cells in normal human breast epithelium. We employed several complementary approaches to identify putative stem cell markers, to characterise an isolated stem cell population and to relate these to cells expressing the steroid receptors ERalpha and PR. Using DNA radiolabelling in human tissue implanted into athymic nude mice, a population of label-retaining cells were shown to be enriched for the putative stem cell markers p21(CIP1) and Msi-1, the human homolog of Drosophila Musashi. Steroid receptor-positive cells were found to co-express these stem cell markers together with cytokeratin 19, another putative stem cell marker in the breast. Human breast epithelial cells with Hoechst dye-effluxing "side population" (SP) properties characteristic of mammary stem cells in mice were demonstrated to be undifferentiated "intermediate" cells by lack of expression of myoepithelial and luminal apical membrane markers. These SP cells were 6-fold enriched for ERalpha-positive cells and expressed several fold higher levels of the ERalpha, p21(CIP1) and Msi1 genes than non-SP cells. In contrast to non-SP cells, SP cells formed branching structures in matrigel which included cells of both luminal and myoepithelial lineages. The data suggest a model where scattered steroid receptor-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells.
Affiliation:
Breast Biology Group, Cancer Research UK Department of Medical Oncology, University of Manchester, Christie Hospital (NHS) Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. rclarke@picr.man.ac.uk
Citation:
A putative human breast stem cell population is enriched for steroid receptor-positive cells. 2005, 277 (2):443-56 Dev. Biol.
Journal:
Developmental Biology
Issue Date:
15-Jan-2005
URI:
http://hdl.handle.net/10541/75866
DOI:
10.1016/j.ydbio.2004.07.044
PubMed ID:
15617686
Type:
Article
Language:
en
ISSN:
0012-1606
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorClarke, Robert B-
dc.contributor.authorSpence, Katherine-
dc.contributor.authorAnderson, Elizabeth-
dc.contributor.authorHowell, Anthony-
dc.contributor.authorOkano, Hideyuki-
dc.contributor.authorPotten, Christopher S-
dc.date.accessioned2009-07-29T14:13:11Z-
dc.date.available2009-07-29T14:13:11Z-
dc.date.issued2005-01-15-
dc.identifier.citationA putative human breast stem cell population is enriched for steroid receptor-positive cells. 2005, 277 (2):443-56 Dev. Biol.en
dc.identifier.issn0012-1606-
dc.identifier.pmid15617686-
dc.identifier.doi10.1016/j.ydbio.2004.07.044-
dc.identifier.urihttp://hdl.handle.net/10541/75866-
dc.description.abstractBreast epithelial stem cells are thought to be the primary targets in the etiology of breast cancer. Since breast cancers mostly express estrogen and progesterone receptor (ERalpha and PR), we examined the biology of these ERalpha/PR-positive cells and their relationship to stem cells in normal human breast epithelium. We employed several complementary approaches to identify putative stem cell markers, to characterise an isolated stem cell population and to relate these to cells expressing the steroid receptors ERalpha and PR. Using DNA radiolabelling in human tissue implanted into athymic nude mice, a population of label-retaining cells were shown to be enriched for the putative stem cell markers p21(CIP1) and Msi-1, the human homolog of Drosophila Musashi. Steroid receptor-positive cells were found to co-express these stem cell markers together with cytokeratin 19, another putative stem cell marker in the breast. Human breast epithelial cells with Hoechst dye-effluxing "side population" (SP) properties characteristic of mammary stem cells in mice were demonstrated to be undifferentiated "intermediate" cells by lack of expression of myoepithelial and luminal apical membrane markers. These SP cells were 6-fold enriched for ERalpha-positive cells and expressed several fold higher levels of the ERalpha, p21(CIP1) and Msi1 genes than non-SP cells. In contrast to non-SP cells, SP cells formed branching structures in matrigel which included cells of both luminal and myoepithelial lineages. The data suggest a model where scattered steroid receptor-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells.en
dc.language.isoenen
dc.subjectOestrogen Receptor alphaen
dc.subject.meshAnalysis of Variance-
dc.subject.meshAnimals-
dc.subject.meshAutoradiography-
dc.subject.meshBreast-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshCell Differentiation-
dc.subject.meshCells, Cultured-
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21-
dc.subject.meshDNA Primers-
dc.subject.meshEpithelial Cells-
dc.subject.meshEstrogen Receptor alpha-
dc.subject.meshFemale-
dc.subject.meshFluorescent Antibody Technique-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKeratins-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshNerve Tissue Proteins-
dc.subject.meshRNA-Binding Proteins-
dc.subject.meshReceptors, Progesterone-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshS Phase-
dc.subject.meshStem Cells-
dc.titleA putative human breast stem cell population is enriched for steroid receptor-positive cells.en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, Cancer Research UK Department of Medical Oncology, University of Manchester, Christie Hospital (NHS) Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK. rclarke@picr.man.ac.uken
dc.identifier.journalDevelopmental Biologyen

Related articles on PubMed

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