| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
ACF-D(I) is a dysplastic lesion which belongs to classical ACF. ACF-D(II) is composed of crypts the as same as or smaller than normal crypts, detected mucin loss, high grade dysplastic lesions, and is hard to detect by classical staining methods but can be detected by a differential staining method (Ochiai et al., Cancer Lett, 220:67-74, 2005). Using a colon cancer model in rodents, I propose that the genesis mechanism of ACF-D(II) be made clear, and study whether ACF-D(II) may be an early lesion of de novo colorectal cancer and the character of that be elucidated. This was analyzed in the points below using colonic lesions of rats induced by azoxymethane.
1. Gene-specific analysis of the genesis mechanism of ACF-D(II) using immunohistochemical analysis.
In all five ACF-D(II) with mucin loss, Muc2 protein, which is major component of mucus in colon, was lost but dystopic expression of Muc5AC protein, which is a major component of mucus in the stomach, was not detected. In ACF-D(II), the expression of Cdx2 protein, which activated gene expression of Muc2 through Muc2 promoter, was almost the same as those in normal crypts and ACF-D(I).
Runx3 is the target of the TGF-β superfamily and a putative tumor suppressor gene. Loss of Runx3 protein was not detected in five ACF-D(I), but detected in all four ACF-D(II). It was suggested that loss of Runx3 protein frequently occurred in ACF-D(II) but not ACF-D(I). Furthermore, it will be verified whether loss of Runx3 protein is specific in ACF-D(II) or not.
2. Comprehensive analysis in genome of the genesis mechanism of ACF-D(II) using array-CGH
In three colon cancers, copy number aberration (CNA) with continuous loss of plural probes was not detected. So it was estimated that CNA may not be detected in ACF-D(II), pre-cancerous lesions in colon.
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