2.50
Hdl Handle:
http://hdl.handle.net/10541/82344
Title:
Steroid receptors and proliferation in the human breast.
Authors:
Clarke, Robert B
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.
Affiliation:
Breast Biology Group, Clinical Research Department, Christie Hospital, Manchester M20 4BX, UK. rclarke@picr.man.ac.uk
Citation:
Steroid receptors and proliferation in the human breast. 2003, 68 (10-13):789-94 Steroids
Journal:
Steroids
Issue Date:
Nov-2003
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
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorClarke, Robert B-
dc.date.accessioned2009-09-23T13:55:45Z-
dc.date.available2009-09-23T13:55:45Z-
dc.date.issued2003-11-
dc.identifier.citationSteroid receptors and proliferation in the human breast. 2003, 68 (10-13):789-94 Steroidsen
dc.identifier.issn0039-128X-
dc.identifier.pmid14667969-
dc.identifier.doi10.1016/S0039-128X(03)00122-3-
dc.identifier.urihttp://hdl.handle.net/10541/82344-
dc.description.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.en
dc.language.isoenen
dc.subjectOestrogen Receptorsen
dc.subjectOestrogen Receptor alphaen
dc.subject.meshAnimals-
dc.subject.meshBreast-
dc.subject.meshCell Differentiation-
dc.subject.meshCell Division-
dc.subject.meshEstrogen Receptor alpha-
dc.subject.meshFemale-
dc.subject.meshKi-67 Antigen-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshMicroscopy, Fluorescence-
dc.subject.meshModels, Biological-
dc.subject.meshProgesterone-
dc.subject.meshReceptors, Estrogen-
dc.subject.meshReceptors, Steroid-
dc.subject.meshTime Factors-
dc.subject.meshTranscription, Genetic-
dc.titleSteroid receptors and proliferation in the human breast.en
dc.typeArticleen
dc.contributor.departmentBreast Biology Group, Clinical Research Department, Christie Hospital, Manchester M20 4BX, UK. rclarke@picr.man.ac.uken
dc.identifier.journalSteroidsen
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