Roles of p51/p63 in the organogenesis, differentiation and carcinogenesis of the urothelium

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Expression profile of p63 in the human urothelial cellsExpression profiles of p63 protein and mRNA in the primary culture of human urothelial cells and human urothelial carcinoma cell lines in vitro were examined using immunocytochemistry and RT-PCR Human urothelial basal cells strongly express ΔNp63 isoform. This ΔNp63 expression was preserved in well differentiated human urothelial carcinoma cell lines, while was impaired in poorly differentiated human urothelial carcinoma cell lines.Expression profile of p63 in normal human urothelial tract and urothelial carcinoma tissueExpression profiles of p63 protein and p63 mRNA isoforms were examined in the normal human urinary tract and human bladder cancer tissues using immunohistochemishy and RT-PCR assay, respectively. In the normal human urinary tract, p63 was expressed in the nucleus of urothelial cells in the basal to intermediate layer and only ΔN isoform was expressed. This expression pattern was preserved in well differentiated, non … More -invasive bladder cancers, while was diminished or disappeared in poorly differentiated, invasive bladder cancers. This in vivo finding was in good agreement with the aforementioned in vitro finding.In the invasive bladder cancer tissue, we found a significant association of decreased ΔNp63 expression with decreased β-catenin expression that has been known to associate with progression of the disease. Since possible role of p63 in the regulation of β-catenin gene expression has been recently suggested, our results indicated that down-regulation of ΔNp63 expression may be one of the causes of β-catenin down regulation.Prognostic significance of ΔNp63 expression in invasive bladder cancerΔNp63 expression was examined in surgically removed invasive bladder cancer tissue. Prognosis of patients with invasive bladder cancer treated with radical cystectomy was analyzed using multivariate analyses. We found that decreased ΔNp63 expression was significant and independent prognostic factors along with pT stage as well as pN stage in these patients. Less