Prostate-specific deletion of Cdh1 induces murine prostatic inflammation and bladder overactivity

<p>Benign Prostatic Hyperplasia (BPH) is an age-related debilitating prostatic disease that is frequently associated with prostatic inflammation and bothersome lower urinary tract symptoms (LUTS). 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 down-regulated in hyperplastic nodules compared to expression in adjacent normal tissues. Here, we explored the potential consequences of prostatic E-cadherin down-regulation on the prostate and bladder <i>in vivo</i> using an inducible murine model of prostate luminal epithelial-specific deletion of <i>Cdh1</i>. The PSA-CreER^T2 transgenic mouse strain expressing tamoxifen-inducible CreER^T2 recombinase driven by a 6-kb human PSA promoter/enhancer was crossed with the B6.129-<i>Cdh1</i>^tm2Kem/J mouse to generate bigenic PSA-CreER^T2/<i>Cdh1</i>^-/- mice. Deletion of E-cadherin was induced by transient administration of tamoxifen when mice reached sexual maturity (7 weeks of age). At 21-23 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 <i>Cdh1</i> deletion had increased prostatic epithelial hyperplasia, inflammation, and stromal changes at 21-23 weeks of age, as well as changes in bladder voiding function compared to age-matched controls. Thus, loss of E-cadherin in the murine prostate could result in prostatic defects that are characteristic of BPH and lower urinary tract symptoms, suggesting that E-cadherin down-regulation could be a driving force in human BPH development and progression.</p>