|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1992 : ¥1,600,000 (Direct Cost : ¥1,600,000)
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.