Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.
Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.
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DOI：
10.1038/sj.bjc.6600764
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发表时间：
2003-03-10
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
P63是p53基因的同系物，被认为对包括尿路上皮在内的层状上皮的正常发育至关重要。为了研究p63在尿路上皮肿瘤发生中的可能作用，我们系统地检测了p63在正常尿路上皮、低级别乳头状非侵袭性（LPN）尿路上皮肿瘤以及高级别或侵袭性癌中的表达，使用非特异性抗体或ΔN-isoform-specific抗体。我们还分析了p63在培养细胞中的表达谱。在检查的组织样本中，这两种抗体的免疫反应性几乎相同。正常尿路上皮基底和中间细胞层显示强烈的核p63免疫染色。这种正常的染色模式在大多数LPN肿瘤中得以保留，而在高级别或肌肉浸润性癌中则经常受损。在mRNA水平上，ΔNp63的表达高于TAp63， ΔNp63 mRNA的表达量与p63的免疫反应性相关，证实ΔNp63与尿路上皮组织中p63的表达有关。在培养细胞中，ΔNp63也在低级别肿瘤细胞和正常尿路上皮细胞中表达，但在高级别侵袭性癌细胞中检测不到。有趣的是，ΔNp63表达受损与β-catenin表达减少显著相关，这可能与尿路上皮肿瘤的进展有关。因此，受损的ΔNp63表达是尿路上皮肿瘤侵袭性表型的特征。
p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a ΔN-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, ΔNp63 expression predominated over TAp63, and amounts of ΔNp63 mRNA correlated with p63 immunoreactivity, confirming that ΔNp63 accounts for p63 expressed in urothelial tissues. In cultured cells, ΔNp63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired ΔNp63 expression significantly associated with reduced β-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired ΔNp63 expression characterises aggressive phenotypes of urothelial neoplasms.
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影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A
影响因子：
15.9
作者：
Conacci-Sorrell, M;Zhurinsky, J;Ben-Ze'ev, A
通讯作者：
Ben-Ze'ev, A
影响因子：
6.5
作者：
Parsa, R;Yang, A;Green, H
通讯作者：
Green, H
DOI：
10.1111/j.1349-7006.2000.tb00961.x
发表时间：
2000-04
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Koga F;Kitahara S;Arai K;Honda M;Sumi S;Yoshida K
通讯作者：
Yoshida K
DOI：
10.1073/pnas.061032098
发表时间：
2001-03-13
影响因子：
11.1
作者：
Pellegrini, G;Dellambra, E;De Luca, M
通讯作者：
De Luca, M