Project/Area Number |
07457310
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cerebral neurosurgery
|
Research Institution | KANAZAWA UNIVERSITY |
Principal Investigator |
YAMASHITA Junkoh Kanazawa University School of Medicine Department of Neurosurgery, Professor, 医学部, 教授 (90026948)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Kazuo Kanazawa University Institute for Gene Research, Director and Professor, 遺伝子実験施設, 施設長教授 (00019879)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1996: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
|
Keywords | triple stranded DNA / anti-gene strategy / retrovirus vector / c-erb B gene / glioma / triplestrandedDNA / anti-genestrategy / retrovirusvector / SP-1 |
Research Abstract |
Anti-gene is a potent inhibitor of transcriptional promoter activity and subsequent gene expression. Since the number of copies of DNA is much fewer than those of transcribed mRNA,anti-gene oligonucleotides targeted against the promoter region would have an advantage over antisense oligonucleotides with an mRNA as a target. This property has been exploited to suppress the expression of a variety of oncogenes for regulating tumor proliferation or viral activities. We developed a novel retroviral vector designed to express human c-erb Banti-gene RNA and to reduce the promoter activity in the cells. Mouse fibroblast NIH3T3 cells were stably transfected with an expression construct containing a truncated human c-erb B gene promoter fused to the firefly luciferase reporter gene. Addition to these cells of the c-erb B anti-gene retroviral vector targeted to the 26 bp pyrimidine-rich element in the human c-erb B gene promoter resulted in a dose-dependent decrease in the luciferase activity of the cells. The results suggest that the reduction of the luciferase activity is due to the effect of the transcribed human c-erb B anti-gene RNA on initiation of transcription of the luciferase gene. The anti-gene RNA produced by a retroviral vector is expected to suppress the expression of an appropriate oncogene and to retard the growth of tumor cells in vivo.
|