Quantitative protein expression profiling of 14-3-3 isoforms in human renal carcinoma shows 14-3-3 epsilon is involved in limitedly increasing renal cell proliferation
Quantitative protein expression profiling of 14-3-3 isoforms in human renal carcinoma shows 14-3-3 epsilon is involved in limitedly increasing renal cell proliferation
复制标题
DOI：
10.1002/elps.200900249
复制
发表时间：
2009-12-01
期刊：
影响因子：
2.9
通讯作者：
Wei, Yuquan
中科院分区：
文献类型：
--
作者：
Liang, Shufang;Xu, Yuhuan;Wei, Yuquan
14-3-3蛋白调节许多与癌症发展有关的细胞过程，并且七种14-3-3同种型在不同肿瘤中具有不同的表达水平和同种型特异性作用。然而，14-3-3蛋白的生物学功能及其与肾癌的相关性至今尚未研究。本研究利用稳定同位素标记技术，通过定量蛋白质组学分析，在细胞培养中发现了14-3-3蛋白在肾癌组织中的表达谱和功能特征。我们发现14-3-3 sigma基因在肾癌组织中表达上调，是正常肾组织的1.44倍，而1.4-3-3 sigma基因在肾癌组织和正常肾组织中几乎未检测到，这是因为我们以前的报道中1.4-3-3 sigma基因的DNA高度甲基化。其他5种亚型在两种状态肾组织中的表达水平基本一致。以下RT-PCR、Western印迹和免疫组织化学分析特异性14-3-3同种型。表达均与定量蛋白质组学数据一致。此外，14-3-3 β在体外过表达可有限地促进肾肿瘤细胞的异常生长。
14-3-3 proteins regulate many cellular processes that are implicated in cancer development, and the seven 14-3-3 isoforms have different expression level and isoform-specific roles in different tumors. However, the biological functions of 14-3-3 proteins and their correlations with renal carcinoma have not been investigated so far. In our study, the expression profiles and functional characterization of 14-3-3 proteins were discovered by a sensitive stable isotope labeling with amino acids in cell culture based quantitative proteomics analysis in human renal carcinoma tissues. We found that 14-3-3 epsilon was up-regulated with 1.44-fold changes in renal cancerous tissues compared with that in counterpart kidney tissues, and 1.4-3-3 sigma was almost not detected in both tissues due to its DNA highly methylated in our previous reports. The other five isoforms almost have similar expression level in two states of renal tissues. The following RT-PCR, Western blot and immunohistochemistry analysis for specific 14-3-3 isoform. expression were all consistent with the quantitative proteomic data. Furthermore, the overexpression of 14-3-3 epsilon in vitro can limitedly prompt the abnormal growth of renal tumor cells.