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Animal models have shown that formalin- and bacterial-induced prostatic inflammation can induce bladder dysfunction; however, the underlying mechanisms contributing to prostatic inflammation in BPH and bladder dysfunction are not clear. We previously reported that E-cadherin expression in BPH is downregulated in hyperplastic nodules compared with expression in adjacent normal tissues. Here, we explored the potential consequences of prostatic E-cadherin downregulation on the prostate and bladder in vivo using an inducible murine model of prostate luminal epithelial-specific deletion of Cdh1. The prostate-specific antigen (PSA)-CreERT2 transgenic mouse strain expressing tamoxifen-inducible CreERT2 recombinase driven by a 6-kb human PSA promoter\/enhancer was crossed with the B6.129-Cdh1tm2Kem\/J mouse to generate bigenic PSA-CreERT2\/Cdh1-\/- mice. Deletion of E-cadherin was induced by transient administration of tamoxifen when mice reached sexual maturity (7 weeks of age). At 21 to 23 weeks of age, the prostate, bladder, and prostatic urethra were examined histologically, and bladder function was assessed using void spot assays and cystometry. Mice with Cdh1 deletion had increased prostatic inflammation, prostatic epithelial hyperplasia, and stromal changes at 21 to 23 weeks of age, as well as changes in bladder voiding function compared with age-matched controls. Thus, loss of E-cadherin in the murine prostate could result in prostatic defects that are characteristic of BPH and LUTS, suggesting that E-cadherin downregulation could be a driving force in human BPH development and progression.<\/jats:p>","DOI":"10.1210\/endocr\/bqaa212","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T05:05:14Z","timestamp":1605848714000},"source":"Crossref","is-referenced-by-count":12,"title":["Prostate-Specific Deletion of <i>Cdh1<\/i> Induces Murine Prostatic Inflammation and Bladder Overactivity"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-1662","authenticated-orcid":false,"given":"Laura E","family":"Pascal","sequence":"first","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora H","family":"Rigatti","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Dhir","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C","family":"de Groat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald B","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Department of Pharmacology and Chemical Biology, and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"issue":"2","key":"2021121701451852000_CIT0001","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ydbio.2014.01.020","article-title":"DNA methylation of E-cadherin is a priming mechanism for prostate development","volume":"387","author":"Keil","year":"2014","journal-title":"Dev Biol."},{"issue":"6","key":"2021121701451852000_CIT0002","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1007\/BF00191218","article-title":"The E-cadherin cell-cell adhesion pathway in urologic malignancies","volume":"13","author":"Morton","year":"1995","journal-title":"World J Urol."},{"issue":"10","key":"2021121701451852000_CIT0003","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1002\/jcp.24596","article-title":"ERK3 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