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Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models.

dc.contributor.author Chen, Ming
dc.contributor.author Yeh, Chiuan-Ren
dc.contributor.author Chang, Hong-Chiang
dc.contributor.author Vitkus, Spencer
dc.contributor.author Wen, Xing-Qiao
dc.contributor.author Bhowmick, Neil A
dc.contributor.author Wolfe, Andrew
dc.contributor.author Yeh, Shuyuan
dc.date.accessioned 2020-04-06T05:54:50Z
dc.date.available 2020-04-06T05:54:50Z
dc.date.issued 2012-01
dc.identifier.issn 0022-3417
dc.identifier.issn 1096-9896
dc.identifier.uri https://hdl.handle.net/10161/20386
dc.description.abstract Squamous metaplasia (SQM) is a specific phenotype in response to oestrogen in the prostate and oestrogen receptor (ER) α is required to mediate this response. Previous studies utilizing tissue recombination with seminal vesicle (SV) mesenchyme and prostatic ductal tips from wild type and ERαKO mice suggested that both epithelial and stromal ERα are necessary for SQM. However, tissue recombination is conducted in the renal capsule of immune-deficient mice, in which the microenvironment is different from normal prostate microenvironment in the intact mice. Furthermore, whether the requirement of stromal ERα in the SV for developing SQM is the same as in the prostate is unknown. Therefore, there is a clear need to evaluate the respective roles of ERα in prostate epithelial versus stromal compartments in the intact mouse. Here we generated a mouse model that has selectively lost ERα in either stromal (FSP-ERαKO) or epithelial prostate cells (pes-ERαKO) to determine the requirements of ERα for oestrogen-stimulated prostate proliferation and SQM. Our results indicated that FSP-ERαKO prostates develop full and uniform SQM, which suggests that loss of the majority (~65%) of stromal ERα will not influence oestrogen-mediated SQM. In contrast, loss of epithelial ERα inhibits oestrogen-mediated prostate growth and SQM evidenced by decreasing cytokertin 10 positive squamous cell stratification and differentiation, by reduced ERα protein expression in SQM compared to wild type mice ERα, and by the presence of normal proliferative activities in the oestrogen-treated pes-ERαKO prostates. These in vivo results suggest that epithelial ERα is required for oestrogen-mediated proliferative response and could be an appropriate target for preventing aberrant oestrogen signalling in the prostate.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof The Journal of pathology
dc.relation.isversionof 10.1002/path.2949
dc.subject Prostate
dc.subject Connective Tissue
dc.subject Epithelium
dc.subject Animals
dc.subject Mice, Knockout
dc.subject Mice
dc.subject Disease Models, Animal
dc.subject Metaplasia
dc.subject Estrogen Receptor alpha
dc.subject Estrogens
dc.subject Immunohistochemistry
dc.subject Cell Proliferation
dc.subject Male
dc.title Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models.
dc.type Journal article
duke.contributor.id Chen, Ming|0914251
dc.date.updated 2020-04-06T05:54:46Z
pubs.begin-page 17
pubs.end-page 27
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Pathology
pubs.organisational-group Duke
pubs.organisational-group Institutes and Centers
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 226
duke.contributor.orcid Chen, Ming|0000-0002-3470-1062


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