| Project/Area Number |
10557127
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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 | 展開研究 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Hyogo Medical University (1999)
Osaka University (1998) |
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Principal Investigator |
ARITA Norio Hyogo College of Medicine, Neurosurgery, Professor, 医学部, 教授 (80159508)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Atsuhisa Hyogo College of Medicine, Neurosurgery, Assistant, 医学部, 助手 (70258151)
MATSUMOTO Tsuyoshi Hyogo College of Medicine, Neurosurgery,Associate Professor, 医学部, 講師 (00181777)
KABA Keizo Hyogo College of Medicine, Neurosurgery, Associate Professor, 医学部, 講師 (70104255)
TOKINO Takashi Sapporo Medical University School of Medicine, Molecular Biology, Professor, がん研, 教授 (40202197)
泉本 修一 大阪大学, 医学部・附属病院, 医員
平賀 章壽 大阪大学, 医学部, 助手 (40243232)
大西 丘倫 大阪大学, 医学部, 助手 (70233210)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | BAI1 / p53 / glioma / glioblastoma / angiogenesis / Tet-On / gene therapy / astrocytoma / angiogenssis |
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| Research Abstract |
BAI1, brain angiogenesis inhibitor 1, was originally isolated as a p53-target gene. BAI1 gene has a p53-binding sequence, and it was directly induced by wild-type p53. BAI1 protein has thrombospondin type 1 repeats which inhibit angiogenesis. In human gliomas, p53 mutation has been frequently observed. It might be possible that in gliomas with mutant p53, BAI1 expression reduced resulting in increased angiogenesis and enhanced tumor growth. We examined relationship between BAI1 expression, p53 mutation and aniogenesis using human glioma tissues. 〔Materials and methods〕 Using human glioma tissues obtained by surgery, (1) expression of the BAI1 gene, (2) mutation of the p53 gene, (3) correlation between BAI1 expression and p53 mutation, and (4) correlation between BAI1 expression and angiogenesis were studied. 〔Results〕 (1) BAI1 mRNA was semiquantitatively assayed by RT-PCR. Compared with that of normal brain tissue, it was reduced in 70% of the glioma examined. BAI1 expression was more
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frequently reduced in high grade gliomas. (2) Mutation of the p53 gene was analyzed by PCR-SSCP. P53 gene was mutated in 30% of the glioma. These mutation occurred in the locus affecting the transcription regulating capacity of the p53 gene. (3)No significant correlation was found between BAI1 expression and p53 mutation. (4) Glioma tissues were immunostained by an anti -CD34 antibody to examine the density of the tumor vessel. In the glioma in which BAI1 expression was reduced, number of the tumor vessels was increased as compared that of the glioma with normal BAI1 expression. 〔Discussion〕 These results indicate that in some glioma, BAI1 expression might be reduced by other factors than p53 mution. BAI1 protein overproduction by BAI1 gene transfer may inhibit angiogenesis in glioma with reduced BAI1 expression. In T98G and U87MG glioma cell lines, BAI1 gene is now tried to be transferred using Tet-On system to investigate how inhibition of the angiogenesis may influence on the glioma cell growth in vivo. Less
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