AuthorsClarke, Robert B
AffiliationBreast Biology Group, Clinical Research Department, Christie Hospital, Manchester M20 4BX, UK. email@example.com
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AbstractDespite recent gains in our knowledge of the hormonal control of proliferation and differentiation in the rodent mammary gland, the factors regulating these processes in the human are poorly understood. We have developed a model in which intact normal human breast tissue is grafted subcutaneously into adult female athymic nude mice and treated with oestrogen (E) and/or progesterone (P) at human physiological serum levels. We have shown that (i) E and not P is the major epithelial cell mitogen in the adult non-pregnant, non-lactating breast, (ii) E induces progesterone receptor (PR) expression and (iii) PR expression is maximally induced at low E concentrations while a higher amount of E is required to stimulate proliferation. These data raised the question of whether one cell type demonstrated two different responses to the two different E concentrations or whether PR expression and proliferation occurred in separate cell populations. Using dual label immunofluorescence, we showed that steroid receptor expression and proliferation (Ki67 antigen) are detected in separate cell populations in normal human breast epithelium, and that cells expressing the oestrogen receptor-alpha (ERalpha) invariably contained the PR. We also reported that this separation between steroid receptor expression and proliferation observed in the normal human epithelium is disrupted at an early stage in breast tumourigenesis. One interpretation supported by our recent findings is that some ERalpha/PR-positive epithelial cells are quiescent breast stem cells that act as "steroid hormone sensors". Such hormone sensor cells might secrete positive or negative paracrine/juxtacrine factors dependent on the prevailing E or P concentration to influence the proliferative activity of adjacent ERalpha/PR-negative epithelial cells.
CitationSteroid receptors and proliferation in the human breast. 2003, 68 (10-13):789-94 Steroids
- Human breast cell proliferation and its relationship to steroid receptor expression.
- Authors: Clarke RB
- Issue date: 2004 Jun
- Ovarian steroids and the human breast: regulation of stem cells and cell proliferation.
- Authors: Clarke RB
- Issue date: 2006 Jul 20
- Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland.
- Authors: Russo J, Ao X, Grill C, Russo IH
- Issue date: 1999 Feb
- 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
- Dissociation between steroid receptor expression and cell proliferation in the human breast.
- Authors: Clarke RB, Howell A, Potten CS, Anderson E
- Issue date: 1997 Nov 15