| Project/Area Number |
17390162
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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 |
Laboratory medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
MAEKAWA Masato Hamamatsu University School of Medicine, 医学部, MD, Professor (20190291)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Akihiro Hamamatsu University School of Medicine, 医学部, Associate Professor (00242769)
IINO Kazumi Hamamatsu University School of Medicine, Hospital, Assistant Professor (90402263)
WATANABE Yoshihisa Hamamatsu University School of Medicine, 医学部, Assistant Professor (00362187)
堀井 俊伸 浜松医科大学, 医学部附属病院, 助手 (80283430)
白井 直人 浜松医科大学, 医学部, 助手 (90362194)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | DNA methylation / Epimutation / Urinary tract cancer / BNIP3 / SARP2 / Methylation analysis / メチル化解祈 / 大腸癌 / hMLH1 / hMSH2 / p16 / 血液悪性腫瘍 / 固形癌 / 遺伝子発現 / 低メチル化 / SNCG / JAK2 / RUNX1 |
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| Research Abstract |
We designed comparative studies of epigenotype and phenotype relationship by using pathological tissues as well as peripheral blood cells, especially in cancer.
Synuclein γ (SNCG) gene expression was down-regulated by DNA methylation and up-regulated by DNA hypomethylation by methylation analysis using cancer cell lines. In leukemia, gastrointestinal cancer and brain tumor, hypomethylation and up-regulation of SNCG was observed. In DNA prepered from peripheral blood of healthy individuals SNCG was methylated and not expressed
Colorectal cancer specimens were analyzed for microsatellite instability and DNA methylation of mismatch repair genes, h MSH2 and hMLH1. No epimutation was discovered
Urinary tract cancer specimens were subjected for DNA methylation and mRNA expression analysis of LDHA LDHB, CKB, CKM, SNCG, MAD2, NPTX2, SARP2, p16, GSTP1 and BNIP3. SARP2 was strongly expressed in normal adjacent tissues but weakly expressed in cancer tissues. Twelve out of 14 cancer tissues and 7 of normal tissues SARP2 was methylated, however, epimutation was not observed in blood leukocytes and urinary sediments. Six out of 14 cancer tissues showed BNIP3 hypemethylation and down-regulation of gene expression Two normal tissues also showed BNIP3 methylation, however, its methylation degree was lower in normal tissues than in cancer tissues.
Epigenotypes regulate tissue-specifically and time-specifically gene expression. However, the regulation mechanism is not uniform but different among cases.
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