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Hepatocarcinogesis and Genomic Instability: Functional Analysis of Y-box binding protein.

肝癌和基因组不稳定性：Y-box 结合蛋白的功能分析。

基本信息

批准号：
12670537
负责人：
KAJINO Kazunori
金额：
$ 2.05万
依托单位：
Japanese Foundation for Cancer Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670537/
关键词：
Hypercarcinogenic State Genomic instability Hepatitles B virus DNA recombination

项目摘要

We isolated dbpA, a member of the Y-box binding protein family, as the candidate for the cellular protein inducing genomic instability. We obtained the following findings about dbpA.1.DbpA expressed in E.coli showed the weak strand exchange activity. Recently, YB-i, another member of this family, is reported to have the annealing activity of DNA or RNA (JBC 276 : 4484 1-44847), and the possible association of this family with DNA recombination is suggested by their work as well as by ours.2.We raised anti-dbpA Ab which recognized dbpA expressed in E.coli with high sensitivity. At present, we are examining the expression of dbpA in various cancer tissue. (In the level of transcripts, the enhanced expression is already confirmed in HCC.)3.We made Transgenic mouse where dbpA is. to be overexpressed in liver. We are going to examine its susceptibility to HCC.4.Using anti-YB-l Ab, we checked its expression in various human tissues. Enhanced expression was detected in several normal tissues including gastrointestinal epithelium, as well as in HCC.5.By replacing T with G at nt -5 of dbpA promoter region, the promoter activity increased twofold. The identical replacement was detected in 3 of 51 HCC cases. We detected the 25 kDa cellular protein which specifically bind to the promoter region with T to A conversion, and currently on the way to identify it.

我们分离了dbpA，Y-盒结合蛋白家族的成员，作为诱导基因组不稳定性的细胞蛋白的候选者。结果表明：1. DbpA在大肠杆菌中表达，具有弱的链交换活性。近年来，该家族的另一个成员YB-1被报道具有DNA或RNA的退火活性（JBC 276：4484 1-44847），他们的工作和我们的工作都表明该家族可能与DNA重组有关。目前，我们正在研究dbpA在各种癌组织中的表达。(In转录物的水平，已经在HCC中证实了增强的表达。3.我们制作了dbpA所在的转基因小鼠。在肝脏中过度表达。4.用抗YB-1抗体检测其在人体不同组织中的表达。5.将dbpA启动子区nt-5的T替换为G后，启动子活性增加了2倍。在51例HCC中，3例检测到相同的替代。我们检测到25 kDa的细胞蛋白，其特异性结合到启动子区域的T到A转换，并且目前正在鉴定它。