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.date.updated

2020-04-06T05:54:46Z

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.identifier.issn

0022-3417

dc.identifier.issn

1096-9896

dc.identifier.uri

https://hdl.handle.net/10161/20386

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.orcid

Chen, Ming|0000-0002-3470-1062

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

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nihms455689.pdf
Size:
4.85 MB
Format:
Adobe Portable Document Format