| Project/Area Number |
15390121
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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 |
Human pathology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
TATEMATSU Masae Aichi Cancer Center, Division of Oncological Pathology, Chief, 腫瘍病理学部, 副所長兼部長 (70117836)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAMOTO Tetsuya Aichi Cancer Center, Division of Oncological Pathology, Section head, 腫瘍病理学部, 室長 (00236861)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2003: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Homeobox genes / Phenotype / Sox2 / Cdx1 / 2 / gastric-and-intestinal mixed phenotype / intestinal metaplasia / gastric cancers / human defensin-5 |
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| Research Abstract |
Intestinal metaplasia(IM) has been extensively studied as a possible premalignant condition in the human stomach. However, many questions remain regarding the pathogenesis of IM development as well as its relationship to gastric cancers. Homeobox genes are very important for the development and maintenance of the organs. In this study, we evaluated the relation between the phenotypes and gastric and intestinal specific transcription factors in IM glands and gastric cancers. The expression of Sox2 as a gastric specific transcription factor was strongly associated with the gastric phenotypic expression such as MUC5AC and MUC6,while Cdx1/Cdx2 as intestinal specific transcription factors had a close relation to intestinal phenotypic expression as MUC2 and villin in both IM glands and gastric cancers. The expression of Sox2 decreased from gastric (G), through gastric-and-intestinal-mixed (GI), to the intestinal (I) phenotypes, while Cdx1/2 were inversely correlated in both IM glands and gastric cancers, independent of the histological types. Cdx2 positive groups had a significant better survival than the negative ones in the advanced gastric cancers. Human defensin-5(HD-5) was a useful Paneth cell differentiation marker, and Paneth cell differentiation of gastric cancer cells did not occur alone, but was accompanied by intestinalization of gastric cancer tissues. Double staining revealed coexistence of MUC5AC- and MUC2/villin/CD10-immunoreactivity in the same cell in GI-IM glands. In conclusions, our results suggest that the expression of gastric and intestinal specific genes is very important for the phenotypic expression of both IM glands and gastric cancer cells. In addition, Cdx2 is a useful prognostic and intestinal phenotypic marker in the advanced gastric cancers. IM may be due to abnormal stem cell differentiation still obeying a certain order.
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