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

p63在人尿路上皮细胞中的表达采用免疫细胞化学和RT-PCR方法检测了p63蛋白和mRNA在体外培养的人尿路上皮细胞和人尿路上皮癌细胞系中的表达。p63在正常人尿路上皮和尿路上皮癌组织中的表达采用免疫组化和RT-PCR方法检测p63蛋白和p63 mRNA在正常人尿路上皮和膀胱癌组织中的表达，分别在正常人尿路上皮细胞中，p63表达于基底层至中间层的细胞核，仅表达ΔN亚型。这种表达模式在高分化、非高分化的乳腺癌中得以保留。 ...更多信息 - 浸润性膀胱癌，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Δ Np 63表达降低与β-catenin表达降低显著相关，已知β-catenin表达降低与疾病进展相关。由于p63在β-catenin基因表达调控中的可能作用最近被提出，我们的研究结果表明Δ Np 63表达的下调可能是β-catenin表达下调的原因之一。采用多因素分析方法对浸润性膀胱癌根治术患者的预后进行分析。我们发现Δ Np 63表达降低是这些患者的显著和独立的预后因素，与pT分期以及pN分期沿着。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