Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models.
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.
Type
Journal articleSubject
ProstateConnective Tissue
Epithelium
Animals
Mice, Knockout
Mice
Disease Models, Animal
Metaplasia
Estrogen Receptor alpha
Estrogens
Immunohistochemistry
Cell Proliferation
Male
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https://hdl.handle.net/10161/20386Published Version (Please cite this version)
10.1002/path.2949Publication Info
Chen, Ming; Yeh, Chiuan-Ren; Chang, Hong-Chiang; Vitkus, Spencer; Wen, Xing-Qiao;
Bhowmick, Neil A; ... Yeh, Shuyuan (2012). Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation
and squamous metaplasia via in vivo tissue selective knockout models. The Journal of pathology, 226(1). pp. 17-27. 10.1002/path.2949. Retrieved from https://hdl.handle.net/10161/20386.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ming Chen
Associate Professor in Pathology
Our laboratory is interested in understanding the molecular and genetic events underlying
cancer progression and metastasis. The focus of our work is a series of genetically
engineered mouse models that faithfully recapitulate human disease. Using a combination
of mouse genetics, omics technologies, cross-species analyses and in vitro approaches,
we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving
metastatic cancer progression, with a long

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