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    Steroid receptors and proliferation in the human breast.

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    Authors
    Clarke, Robert B
    Affiliation
    Breast Biology Group, Clinical Research Department, Christie Hospital, Manchester M20 4BX, UK. rclarke@picr.man.ac.uk
    Issue Date
    2003-11
    
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    Abstract
    Despite 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.
    Citation
    Steroid receptors and proliferation in the human breast. 2003, 68 (10-13):789-94 Steroids
    Journal
    Steroids
    URI
    http://hdl.handle.net/10541/82344
    DOI
    10.1016/S0039-128X(03)00122-3
    PubMed ID
    14667969
    Type
    Article
    Language
    en
    ISSN
    0039-128X
    ae974a485f413a2113503eed53cd6c53
    10.1016/S0039-128X(03)00122-3
    Scopus Count
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