| First Author | Chen M | Year | 2012 |
| Journal | J Pathol | Volume | 226 |
| Issue | 1 | Pages | 17-27 |
| PubMed ID | 22069040 | Mgi Jnum | J:180158 |
| Mgi Id | MGI:5305535 | Doi | 10.1002/path.2949 |
| Citation | Chen M, et al. (2012) Loss of epithelial oestrogen receptor alpha inhibits oestrogen-stimulated prostate proliferation and squamous metaplasia via in vivo tissue selective knockout models. J Pathol 226(1):17-27 |
| abstractText | Squamous metaplasia (SQM) is a specific phenotype in response to oestrogen in the prostate and oestrogen receptor (ER) alpha is required to mediate this response. Previous studies utilizing tissue recombination with seminal vesicle (SV) mesenchyme and prostatic ductal tips from wild type and ERalphaKO mice suggested that both epithelial and stromal ERalpha 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 ERalpha 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 ERalpha in prostate epithelial versus stromal compartments in the intact mouse. Here we generated a mouse model that has selectively lost ERalpha in either stromal (FSP-ERalphaKO) or epithelial prostate cells (pes-ERalphaKO) to determine the requirements of ERalpha for oestrogen-stimulated prostate proliferation and SQM. Our results indicated that FSP-ERalphaKO prostates develop full and uniform SQM, which suggests that loss of the majority (~65%) of stromal ERalpha will not influence oestrogen-mediated SQM. In contrast, loss of epithelial ERalpha inhibits oestrogen-mediated prostate growth and SQM evidenced by decreasing cytokertin 10 positive squamous cell stratification and differentiation, by reduced ERalpha protein expression in SQM compared to wild type mice ERalpha, and by the presence of normal proliferative activities in the oestrogen-treated pes-ERalphaKO prostates. These in vivo results suggest that epithelial ERalpha is required for oestrogen-mediated proliferative response and could be an appropriate target for preventing aberrant oestrogen signalling in the prostate. |
