Overexpression of the wild type p73 gene in human bladder cancer

Overexpression of the wild type p73 gene in human bladder cancer
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DOI:
10.1038/sj.onc.1202474
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发表时间:
1999-02-25
期刊:
影响因子:
8
通讯作者:
Liu, WG
Liu, WG
中科院分区:
医学1区
文献类型:
--
作者:
Yokomizo, A;Mai, M;Liu, WG

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p73是第一个p53相关基因,最近被鉴定并显示在许多不同的人体组织中单等位基因表达。为了确定该基因在人膀胱癌中的潜在作用,我们研究了p73表达水平,等位基因表达模式,并分析了23例原发性浸润性膀胱癌与匹配的正常组织和7个膀胱癌细胞系中的p73突变。在使用定量RT-PCR分析的正常和特纳组织之间的比较中,我发现p73在22/23的膀胱癌中过表达,有时高达20倍。等位基因表达分析使用外显子2的C/T多态性和新发现的外显子5的T/C多态性显示,p73在正常膀胱和癌组织中双等位基因表达,表明p73在膀胱组织中没有印记。应用变性高效液相色谱分析和DNA测序技术对膀胱癌DNA中p73基因进行突变筛查,结果显示p73基因的任何编码外显子均未发生肿瘤特异性突变。这些数据表明,p73不太可能是肿瘤抑制基因,但p73的过度表达可能与膀胱癌的发生有关。
p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and turner tissues using quantitative RT-PCR analysis, me found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene, These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.