| Project/Area Number |
12671221
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Mie University |
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Principal Investigator |
MIKI Chikao (2001-2002) Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50242962)
山本 隆行 (2000) 三重大学, 医学部, 助手 (20283541)
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| Co-Investigator(Kenkyū-buntansha) |
NOBORI Tsutomu Mie University, Faculty of Medicine, Professor, 医学部, 教授 (60106995)
三木 誓雄 三重大学, 医学部, 助教授 (50242962)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | MAD2 / chromosomal instability / promoter / hypermethylation / 一塩基多型 / CIN / 塩基配列 / 免疫組織化学 |
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| Research Abstract |
Several genes were known to be involved in chromosomal instability in cancer. Among them, MAD2 gene plays an important role in binding of spindle fibers to the centromeric region of each chromosome. To date, no mutations were found in MAD2 gene. Recently, lower expression of MAD2 was reported to be related with chromosomal instability. Therefore, chromosomal instability will be caused by haploinsufficiency, in which the protein level is halved and is much lower than needed. We have searched for the mutation of MAD2 gene in the gastrointestinal cancers, but found no mutations. We then performed a luciferase reporter assay using the promoter of MAD2 gene containing novel single nucleotide polymorphism (SNP). The results indicated that this SNP did not affect the MAD2 promoter activity at all. Since promoter hypermethylation is an epigenetic mechanism for silencing the gene, we developed the methylation specific PCR assay for MAD2 promoter. MAD2 promoter was found to be methylated even in peripheral blood mononuclear cells from healthy subjects. Accordingly, it is important to determine which CpG dinucleotides in the promoter are methylated and to correlate the promoter activity with the site of methylation. Moreover, the MAD2 protein level detected by immunostaining were found to be a marker for hepatic metastasis in gastric cancers.
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