2003 Fiscal Year Final Research Report Summary
Genomic analysis of mutational genetic events in the genes involved in gastroenterological cancer progression.
| Project/Area Number |
13470114
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ABURATANI Hiroyuki The University of Tokyo, Center for Collaborative Research, Professor, 国際・産学共同研究センター, 教授 (10202657)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Tatsuhiko The University of Tokyo, Research Center for Advanced Science and Technology, Professor, 先端科学技術研究センター, 教授 (90170266)
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| Project Period (FY) |
2001 – 2003
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| Keywords | gene expression profiles / LOH / genomic analysis / cluster analysis / liver cancer / gastric cancer |
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| Research Abstract |
To understand the multi-step carcinogenesis process, we have applied transcriptome analysis and genomic analysis to collect comprehensive biological information, then developed novel data analysis algorithms for mining such huge amount of data.
1) Molecular signature based on differentiation grade of hepatocellular carcinoma (HCC)
We applied the EIM (Expression Imbalance Map) to detect the chromosomal bias in gene expression profiles. The results were well correlated with previous reports by CGH and was also confirmed by quantitative PCR. We assume gene dosage has a significant effect on the gene expression profiles. We also observed chromosomal aberrations accumulate during the dedifferentiation process.
We demonstrated GPC3 protein level is elevated in HCCs as well as its RNA level. GPC3 inhibits BMP-7 signaling through the Smad pathway by reporter gene assay.
2) Molecular and functional analysis of the genes involved in gastric cancer progression
To gain molecular understanding of carcinogenesis, progression, and diversity of gastric cancer, 22 primary human advanced gastric cancer tissues and 8 noncancerous gastric tissues were analyzed by high-density oligonucleotide microarray in this study. These results provide not only a new molecular basis for understanding biological properties of gastric cancer, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric cancer.
We performed global analysis on differential gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its derivative sublines with high potential for metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes (OCUM-2MLN) We observed preferential up-regulation of trefoil factor 1, alpha-1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells prone to peritoneal dissemination. Induction of Galectin4 in Tet-inducible Galectin4 expression cell line, MKN74TetOff-g4, elevation of mobility and invasion were observed.
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[Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer. 103(4). 455-465 (2003)
Description
「研究成果報告書概要(和文)」より
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[Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer. 103(4). 455-465 (2003)
Description
「研究成果報告書概要(欧文)」より
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