| Project/Area Number |
14570135
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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 |
Human pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
UOZAKI Hiroshi (2004) The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10296246)
鄭 子文 (2002-2003) 東京大学, 大学院・医学系研究科, 講師 (90285768)
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| Co-Investigator(Kenkyū-buntansha) |
FUKAYAMA Masashi The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70281293)
SHIBAHARA Junji The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60334380)
宇於崎 宏 東京大学, 医学部附属病院, 助手 (10296246)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Gastric cancer / 11p15 / MUC / Epstein-Barr virus / Fetal stomach / 11q15 |
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| Research Abstract |
We investigated the chromosome 11p15 locus of gastric cancer (GC). The 11p15 locus was focused through Genechip TM assay of SCID mouse transplantable Epstein-Barr virus (EBV)-associated GC strain. In this study, MUC genes were focused among the genes located on 11p15. Expression of MUC2,5AC, and 6 determinates mucin phenotype of GC ; gastric type, intestinal type, mixed type, and null type.
We examined 74 cases of GC immunohistochemically and found that EBVaGC is likely to be null phenotype and gastric phenotype. It is a contrast to EBV negative GC, almost of which shows either gastric or intestinal phenotype. EBVaGC shows decrease of CK7 expression immunohistochemically. From both results of mucin and cytokeratin expression, EBVaGC is thought to be close to stem cells of gastric mucosa.
Next we examined DNA methylation status of MUC2 and MUC5AC genes by digestion with methylation sensitive restricted enzyme, HpaII, followed by PCR Among 22 GC cases, 8 cases were MUC2 positive and 11 cases MUC5AC positive immunohistochemically. Whereas all cases showed methylated status of MUC2 and MUC5AC gene. There were no correlation between immunohistochemical positivity and DNA methylation status of MUC2 and 5AC.
We examined 6 GC cell lines. We have got EBV infected sublines of all 6 cell lines using recombinant EBV. Immunocytochemically TMK1 decrease MUC2 after EBV infection. It was not associated with change of DNA methylation status. MUC5AC expression was not influenced by EBV infection, but TMK1, MKN-1, and NU-GC-3 increased DNA methylation at MUC5AC locus after EBV infection. The result of the cell line study is consistent with the fact that EBVaGC shows high rate of DNA methylation of tumor related genes.
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