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

用免疫细胞化学和RT-PCR法检测原代培养的人尿路上皮细胞和体外培养的人尿路上皮癌细胞株中p63蛋白和p63基因的表达谱。人尿上皮细胞强表达ΔNp63亚型。P63在正常尿路上皮细胞和尿路上皮癌组织中的表达谱采用免疫组织化学和RT-Δ方法分别检测正常尿路和膀胱癌组织中p63蛋白和p63mR NA亚型的表达。在正常人尿路组织中，p63表达于尿路上皮细胞核的基底层至中层，仅表达ΔN亚型。这种表达模式在分化良好的非…中得以保留更具侵袭性的膀胱癌，而在低分化浸润性膀胱癌中减少或消失。在浸润性膀胱癌组织中，我们发现ΔNp63表达降低与β-连环蛋白表达降低显著相关，这已被认为与疾病的进展有关。鉴于p63在β-连环蛋白基因表达调控中的可能作用，我们的研究结果表明，ΔNp63表达下调可能是β-连环蛋白表达下调的原因之一。对浸润性膀胱癌根治术患者的预后进行多因素分析。我们发现，在这些患者中，ΔNp63表达的降低与PT分期和PN分期一起是显著的独立预后因素。较少

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