Project/Area Number |
13470043
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human pathology
|
Research Institution | Gifu University |
Principal Investigator |
MORI Hideki MD. PhD., Gifu Univ. Sch. Med. Dept. Pathol., Professor, 医学部, 教授 (70021433)
|
Co-Investigator(Kenkyū-buntansha) |
HIROSE Yoshinobu MD. PhD., Gifu Univ. Sch. Med. Dept. Pathol., Assistant professor, 医学部附属病院, 助手 (20293574)
YOSHIMI Naoki MD. PhD., Univ. Ryukyus, Dept. Pathol., Professor, 医学部, 教授 (30166996)
YAMADA Yasuhiro MD. PhD., Gifu Univ. Sch. Med. Dept. Pathol., Assistant professor, 医学部, 助手 (70313872)
HARA Akira MD. PhD., Gifu Univ. Sch. Med. Dept Pathol., Associate professor, 医学部, 助教授 (10242728)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥8,000,000 (Direct Cost: ¥8,000,000)
|
Keywords | Colon cancer / Premalignant lesion / β-Catenin / APC / BCAC / ACF / 大腸発癌 / β-catenin |
Research Abstract |
It is widely believed that colorectal carcinogenesis is a representative multistep tumorigenesis with events of genetic alterations. Aberrant crypt foci (ACF) recognized in the surface of cancer-predisposed colons of rodents have been regarded as early-appearing preneoplastic lesions. However, it is not clear that such lesions are truly precancerous lesions for colorectal cancers in rodents. Recently, we have identified β-catenin-accumulated crypts (BCAC) in colonic mucosa at the early stages of colon carcinogenesis. In this project, we performed further analyses of BCAC in rodents. We demonstrated that alterations in Wnt signaling pathway result in the formation of BCAC, and BCAC play an important role during early stages of colon carcinogenesis. Our results provide additional evidences that BCAC are premalignant lesions of colon cancer in rodents. We also showed that BCAC are reliable biomarkers for colon carcinogenesis. In addition, we searched for the similar dysplastic lesions as BCAC in human colon. We investigated a large number of histological sections from human colons. However, such lesions confirmed in rodents have not yet identified in human colonic mucosa. Now, we are going on further analyses to find out BCAC in human colon. We determined mutation spectrum of APC gene in small human colonic polyps and got some interesting results. Although the results are preliminary, we believe that such data provide important clue to understand the premalignancy of colon cancer in humans as well as rodents.
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