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1. 发明申请

WO2005113824A2 PROTEIN TYROSINE PHOSPHATASE MUTATIONS IN CANCERS 审中-公开
标题翻译：蛋白质酪氨酸磷酸酶突变体
公开(公告)号：WO2005113824A2
公开(公告)日：2005-12-01
申请号：PCT/US2005/017105
申请日：2005-05-16
申请人： WANG, Zhenghe , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： WANG, Zhenghe , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12N9/16 , C12Q2600/112 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Y301/03048 , G01N33/5011 , G01N2333/916
摘要： Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs ( PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14 ) affecting 26 % of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP ( PTPRP ) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.
摘要翻译：由蛋白酪氨酸磷酸酶（PTP）和激酶（PTK）调节的酪氨酸磷酸化在肿瘤发生的信号通路中是重要的。人类癌症中酪氨酸磷酸酶基因超家族的突变分析鉴定了影响26％结肠直肠癌和较小部分肺癌，乳腺癌和胃癌的6种PTPs（PTPRF，PTPRG，PTPRT，PTPN3，PTPN13，PTPN14）中的83个体细胞突变。十五个突变是无义，移位或剪接位点改变，预计会导致截短的蛋白质缺乏磷酸酶活性。在生物化学检查中发现最常改变的PTP（PTPRP）中的五个错义突变被发现可以降低磷酸酶活性。野生型但不是突变PTPRT在人类癌细胞中的表达抑制细胞生长。这些观察表明，酪氨酸磷酸酶基因是肿瘤抑制基因，调节可能适合于治疗性干预的细胞途径。

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