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

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 in vivo using an inducible murine model of prostate luminal
epithelial-specific deletion of Cdh1. The 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 21-23 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 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.