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.

在本研究项目中，我们研究了癌基因家族mycs，特别是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。神经母细胞瘤中N-myc基因扩增程度与恶性程度存在相关性，表明基因扩增的测量可能具有作为肿瘤标志物的意义。本研究旨在揭示N-myc基因的调控机制首先研究了位于N-myc基因5'侧翼区域的癌基因表达的转录调控区。到1992年，在扩增了N-myc基因的TNB9神经母细胞瘤细胞中，包括5'侧翼区的N-myc基因被克隆并测序。 1992年和1993年，为了鉴定控制区，使用TNB9的N-myc基因衍生的质粒进行了报告基因测定。新构建了具有CAT基因作为报告基因和不同长度的5'侧翼区的质粒，并研究了作为N-myc表达细胞的GOTO神经母细胞瘤细胞和作为N-myc非表达细胞的HeLaS3细胞中的CAT活性。在 N-myc 表达细胞中发现转录促进和抑制区域，在 N-myc 非表达细胞中发现转录促进区域。 N-myc 表达细胞中可能有不止一种转录因子调节 N-myc 基因转录。各种恶性肿瘤中因子的克隆和因子异常的进一步研究是必要的。