The transcription factors regulate a tumor maker gene, Glutathione Transferase P.

转录因子调节肿瘤标记基因谷胱甘肽转移酶 P。

基本信息

批准号：
06807012
负责人：
SAKAI Masaharu
金额：
$ 1.28万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807012/
关键词：
Glutathione transferase P Rat hepatocarcinogenesis Tumor maker Transcriptional control Jun Fos PPAR Maf 転写制御 NQO遺伝子グルタチオントランスフェラーゼP(GST-P)癌遺伝子 maf関連遺伝子 bZip構造

项目摘要

In multi-step tumorigenesis, change in the pattern of gene expression might be an important step, as well as the steps of oncogene activation and/or inactivation of anti-oncogene. To investigate the possible alteration of the cellular pattern of gene expression during neoplastic transformation, it may be useful to explore tumor maker gene as one of the tools. From this view point, we have been studying the regulation mechanism of glutathione transferase P (GST-P) gene during chemical hepatocarcinogenesis of the rat, and obtained following results.1 Jun and Fos related factors : GST-P gene has multiple TRE-like elements and is activated by Jun and Fos. All of related to these factors bind and modulate the GST-P expression. FosB and dFosB were repressed the GST-P expression.2 Peroxisome proliferators suppressed the GST-P expression : Peroxisome proliferator activated receptor (PPAR) interacts with Jun and inhibits the GST-P expression. PPAR expression was decreased in the early stages of hepatocarcinogenesis of the rat. This suggests PPAR functions, at least in part, to the derepression of the GST-P gene in early stage of neoplastic transformation.3 The TRE sequence located on the promoter of the GST-P gene is also binding consensus sequence of the transcription factor Maf. We have obtained the results that indicate the Maf binds to GST-P promoter and activates GST-P gene strongly. However, since the observation that the expression of GST-Pgene and Maf was not correlated during hepatocarcinogenesis, Maf is not the main regulator of GST-P expression in early stages of carcinogenesis. Gel mobility shift analysis using nuclear extracts from the liver bearing hyperplastic nodules and transfection analysis using dominant-negative genes of maf, suggest that some Maf related factor (s) activate GST-P gene.

在多步肿瘤发生中，基因表达模式的变化可能是一个重要的步骤，也是癌基因激活和/或抗癌基因灭活的步骤。为了研究肿瘤转化过程中基因表达的细胞表达的可能改变，探索肿瘤制造子基因作为工具之一可能是有用的。从这个角度来看，我们一直在研究大鼠化学肝癌发生期间谷胱甘肽转移酶P（GST-P）基因的调节机制，并获得了遵循结果。1Jun和FOS相关因素：GST-P基因具有多个TRE样基因。元素，由Jun和Fos激活。所有与这些因素有关的所有有关的结合并调节GST-P表达。 FOSB和DFOSB被抑制GST-P表达。2过氧化物酶体增殖物抑制了GST-P表达：过氧化物酶体增殖物激活受体（PPAR）与JUN相互作用并抑制GST-P表达。在大鼠的肝癌发生的早期，PPAR表达降低。这表明PPAR的功能至少部分地表明在肿瘤转化的早期阶段GST-P基因的压抑。3位于GST-P基因启动子上的TRE序列也是转录因子MAF的结合共识序列。我们获得了指示MAF与GST-P启动子结合并强烈激活GST-P基因的结果。但是，由于观察到肝癌发生期间GST-PGENE和MAF的表达没有相关性，因此MAF并不是癌变早期阶段GST-P表达的主要调节剂。使用来自肝轴承增生结节的核提取物和使用MAF的显性阴性基因转染分析的凝胶迁移率转移分析，这表明某些MAF相关因子激活GST-P基因。