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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.

Publication ,  Journal Article
Chen, M; Yeh, C-R; Chang, H-C; Vitkus, S; Wen, X-Q; Bhowmick, NA; Wolfe, A; Yeh, S
Published in: J Pathol
January 2012

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.

Duke Scholars

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

January 2012

Volume

226

Issue

1

Start / End Page

17 / 27

Location

England

Related Subject Headings

  • Prostate
  • Pathology
  • Mice, Knockout
  • Mice
  • Metaplasia
  • Male
  • Immunohistochemistry
  • Estrogens
  • Estrogen Receptor alpha
  • Epithelium
 

Citation

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MLA
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Chen, M., Yeh, C.-R., Chang, H.-C., Vitkus, S., Wen, X.-Q., Bhowmick, N. A., … Yeh, S. (2012). Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. J Pathol, 226(1), 17–27. https://doi.org/10.1002/path.2949
Chen, Ming, Chiuan-Ren Yeh, Hong-Chiang Chang, Spencer Vitkus, Xing-Qiao Wen, Neil A. Bhowmick, Andrew Wolfe, and Shuyuan Yeh. “Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models.J Pathol 226, no. 1 (January 2012): 17–27. https://doi.org/10.1002/path.2949.
Chen M, Yeh C-R, Chang H-C, Vitkus S, Wen X-Q, Bhowmick NA, Wolfe A, Yeh S. Loss of epithelial oestrogen receptor α inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. J Pathol. 2012 Jan;226(1):17–27.
Journal cover image

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

January 2012

Volume

226

Issue

1

Start / End Page

17 / 27

Location

England

Related Subject Headings

  • Prostate
  • Pathology
  • Mice, Knockout
  • Mice
  • Metaplasia
  • Male
  • Immunohistochemistry
  • Estrogens
  • Estrogen Receptor alpha
  • Epithelium