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IDENTIFICATION OF A TRANSCRIPTION-REGULATING FACTOR FOR NUCLEAR ONCOGENES AND ITS APPLICATION FOR DIAGNOSIS

核癌基因转录调控因子的鉴定及其诊断应用

基本信息

批准号：
04670753
负责人：
HEMMI Hiromichi
金额：
$ 1.34万
依托单位：
TOHO 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：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670753/
关键词：
myc oncogenes N-myc oncogene transcription factor transcription control region 5'-flanking region 発現制御領域 5′-flanking regin 発現制御因子 5´-flanking region BIAtore system スクリーニング

项目摘要

In this research porject, we studied the mechanism of expression of an oncogene family, mycs, especially N-myc. The regulatory mechanism of the myc gene transcription is unclear. The myc gene products (c-Myc, N-Myc, and L-Myc) forming hetrodimers with Max are known as transcription factors, though the target gene of the myc gene family are not known, yet. Gene amplification of the myc gene family is also known in certain malignant tumors. There is a correlation between the extent of the N-myc gene amplification and the malignancy in neuroblastoma, indicating that the measurement of the gene amplification potentially has a significance as a tumor maker.In this study, to reveal the regulatory mechanism of N-myc oncogene expression, the transcription regulatory region located at 5'-flanking region of N-myc gene was first investigated. By 1992, N-myc gene including 5'-flanking region in TNB9 neuroblastoma cells of which N-myc gene is amplified was cloned and sequenced. In 1992 and 1993, to identify the control region, a reporter gene assay was carried out using the plasmids derived from N-myc gene of TNB9. Plasmids having CAT gene as a reporter gene and various length of 5'-flanking region, was newly constructed and studied the CAT activity in GOTO neuroblastoma cells as N-myc expressing cells and in HeLaS3 cells as N-myc non-expressing cells. The transcription-promoting and repressing regions were found in N-myc expressing cells and transcription-promoting regions were found in N-myc non-expressing cells. It is likely that there are more than one transcription factors regulating N-myc gene transcription in N-myc expressing cells. The cloning of the factor(s) and further investigation of abnormality of the factor(s) in various malignant tumor are neccessary.

本研究课题研究了癌基因家族myc，尤其是N-myc的表达机制。myc基因转录的调控机制尚不清楚。与Max形成异二聚体的myc基因产物（c-Myc、N-Myc和L-Myc）被称为转录因子，尽管myc基因家族的靶基因尚不清楚。myc基因家族的基因扩增在某些恶性肿瘤中也是已知的。N-myc基因扩增的程度与神经母细胞瘤的恶性程度有关，表明检测N-myc基因扩增可能具有作为肿瘤标志物的意义，为了揭示N-myc癌基因表达的调控机制，本研究首先研究了位于N-myc基因5 '端的转录调控区。到1992年，在扩增出N-myc基因的TNB 9神经母细胞瘤细胞中，克隆了N-myc基因及其5 '侧翼区，并进行了序列测定。在1992年和1993年，为了鉴定对照区，使用来自TNB 9的N-myc基因的质粒进行报告基因测定。以CAT基因为报告基因，5 ′-侧翼区为不同长度的质粒，在N-myc表达细胞后藤神经母细胞瘤细胞和非N-myc表达细胞HeLaS 3中研究了CAT活性。在N-myc表达细胞中发现了转录促进区和转录抑制区，而在N-myc非表达细胞中发现了转录促进区。在表达N-myc的细胞中，可能存在不止一种转录因子调节N-myc基因的转录。因此，克隆该因子并进一步研究其在各种恶性肿瘤中的异常是必要的。