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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.

在多步骤肿瘤发生中，基因表达模式的改变可能是重要的一步，癌基因激活和/或抑癌基因失活也可能是重要的一步。为了研究肿瘤转化过程中基因表达的细胞模式的可能变化，探索肿瘤标志物基因作为工具之一可能是有用的。从这一角度出发，我们对谷胱甘肽转移酶P(GST-P)基因在大鼠化学性肝癌发生过程中的调控机制进行了研究，得到了以下结果：1.Jun和Fos相关因子：GST-P基因具有多个TrE样元件，并被Jun和Fos激活。所有这些因素都与GST-P的表达密切相关。2过氧化体增殖物抑制GST-P的表达：PPAR与Jun相互作用，抑制GST-P的表达。在大鼠肝癌发生的早期，PPAR的表达降低。这表明PPAR至少部分地在肿瘤转化的早期阶段对GST-P基因的去抑制起作用。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。结果表明，MAF与GST-P启动子结合，对GST-P基因有较强的激活作用。然而，由于观察到GST-P基因的表达与MAF在肝癌发生过程中没有相关性，MAF在肝癌发生的早期阶段不是GST-P表达的主要调节因子。应用肝细胞增生性结节细胞核提取液的凝胶迁移率分析和MAF显性-阴性基因的转染分析表明，某些MAF相关因子(S)激活了GST-P基因。