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

Robert B. Clarke, Katherine Spence, Elizabeth Anderson, Anthony Howell, Hideyuki Okano, Christopher S. Potten

Research output: Contribution to journalArticle

263 Citations (Scopus)

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 (ERα and PR), we examined the biology of these ERα/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 ERα 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 ERα-positive cells and expressed several fold higher levels of the ERα, 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.

Original languageEnglish
Pages (from-to)443-456
Number of pages14
JournalDevelopmental Biology
Volume277
Issue number2
DOIs
Publication statusPublished - 2005 Jan 15

Fingerprint

Steroid Receptors
Breast
Stem Cells
Population
Side-Population Cells
Progesterone Receptors
Nude Mice
Estrogen Receptors
Epithelial Cells
Asymmetric Cell Division
Breast Neoplasms
Keratin-19
Population Characteristics
Drosophila
Coloring Agents
Epithelium
Membranes

Keywords

  • Cancer
  • Differentiation
  • Epithelium
  • Msi1
  • Normal breast
  • P21
  • Side population cells
  • Stem cells
  • Steroid receptors

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A putative human breast stem cell population is enriched for steroid receptor-positive cells. / Clarke, Robert B.; Spence, Katherine; Anderson, Elizabeth; Howell, Anthony; Okano, Hideyuki; Potten, Christopher S.

In: Developmental Biology, Vol. 277, No. 2, 15.01.2005, p. 443-456.

Research output: Contribution to journalArticle

Clarke, Robert B. ; Spence, Katherine ; Anderson, Elizabeth ; Howell, Anthony ; Okano, Hideyuki ; Potten, Christopher S. / A putative human breast stem cell population is enriched for steroid receptor-positive cells. In: Developmental Biology. 2005 ; Vol. 277, No. 2. pp. 443-456.
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