2007 Fiscal Year Final Research Report Summary
Research on premalignant lesions using beta-catenin/Tcfreporter mice
| Project/Area Number |
17390112
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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 |
Experimental pathology
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| Research Institution | Gifu University |
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Principal Investigator |
MORI Hideki Gifu University, Graduate School of Medicine, Professor (70021433)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Yasuhiro Gifu University, Graduate School of Medicine, Lecturer (70313872)
HIROSE Yoshinobu Gifu University, Hospital, Associate professor (20293574)
MATSUNAGA Kengo Gifu University, Hospital, Assistant professor (00402173)
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| Project Period (FY) |
2005 – 2007
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| Keywords | beta-catenin / tcf / gastric cancer / colon cancer / premalignant lesion |
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| Research Abstract |
Apc ^(min/+) mouse, a mouse model for human familial adenomatosis polyposis (FAP), contains a truncating mutation in the Apc gene and spontaneously develops intestinal tumors. Our previous study revealed two distinct stages of tumorigenesis in the colon of Apc^<Min/+> mouse ; microadenomas and macroscopic tumors. Microadenomas already have lost their remaining allele of the Apc and all microadenomas show accumulation of β-catenin, indicating that activation of the canonical Wnt pathway is an initiating event in the tumorigenesis. This study shows that expression of nuclear β-catenin in macroscopic tumors is further upregulated in comparison with that in microadenomas. Furthermore, transcriptional activity of β-catenin/T-cell factor (Tcf) signaling, assessed using β-catenin/Tcf reporter transgenic mice is higher in the macroscopic tumors than that in microadenomas. In addition, the expression level of Dickkopf-1 (Dick1), which is known to be a negative modifier of the canonical Wnt pathway, was reduced only in colon tumors. These results suggest that activation of β-catenin/Tcf transcription plays a role, not only in the initiation stage, but also in the promotion stage of colon carcinogenesis in Apc ^(Min/+) mice. We further demonstrated that the gastric tumors developed in Apc^(Mini/+) mice express higher β-catenin/Tcf transcriptions, thus suggesting that the canonical Wnt signaling is involved in gastric carcinogenesis as well.
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