1996 Fiscal Year Final Research Report Summary
Inhibition of Gene Expression from the Human c-erb B Gene Promoter by a Retroviral Vector Expressing Anti-gene RNA
| Project/Area Number |
07457310
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
YAMASHITA Junkoh Kanazawa University School of Medicine Department of Neurosurgery, Professor, 医学部, 教授 (90026948)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Keywords | triple stranded DNA / anti-gene strategy / retrovirus vector / c-erb B gene / glioma |
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| 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.
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[Publications] Yamashima T,Saido T,Takita M,Miyazawa A,Yamano J,Miyakawa A,Nishijo H,Yamashita J,Kawashima S,Ono T,Yoshioka T: "Transient brain ischemia provokes Ca2+, PIP2 and calpain responses prior to delayd neuronal death in monkeys" Eur J Neurosci. 8. 1932-1944 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Sakuda K,Kohda Y,Matsumoto T,Park C,Seto A,Tohma Y,Hasegawa M,Kida S,Nitta H,Yamashima T,Yamashita J: "Expression of NF2 gene product merlin in arachnoid villi and meningiomas" Brain Tumor Pathol. 13. 145-148 (1996)
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「研究成果報告書概要(欧文)」より
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