| Project/Area Number |
14370119
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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 |
Hygiene
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
YUASA Yasuhito Tokyo Medical and Dental University, Department of Molecular Oncology, Professor, 大学院・医歯学総合研究科, 教授 (80111558)
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| Co-Investigator(Kenkyū-buntansha) |
AKIYAMA Yoshimitsu Tokyo Medical and Dental University, Department of Molecular Oncology, lecturer, 大学院・医歯学総合研究科, 講師 (80262187)
三宅 智 東京医科歯科大学, 大学院・医歯学総合研究科, 講師 (00332346)
丸山 和夫 東京医科歯科大学, 大学院・医歯学総合研究科, 助教授 (90165944)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | gastric cancer / homeoprotein / CDX2 / methylation / diet / transcription / PDX1 / SOX2 / 腸上皮化生 / 転写因子 |
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| Research Abstract |
1. We analyzed the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the lifestyle of the patients. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and 1 (6.7%) of the 15 female patients. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and with full or overeating habits. We also analyzed the methylation status of p16/INK4a and hMLHI, but their frequencies were not associated with lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes and the resultant aberrant expression of genes involved in carcinogenesis.
2. p21/WAF1 is a cyclin-dependent kinase inhibitor. CDX2 transactivated and physically interacted with the promoter of p21 in a p53-independent manner. Overexpression of CDX2 increased p21 rnRNA. These data suggest that p21 is a transcriptional target of CDX2.
3. We investigated expression of PDX 1, which contributes to development o
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f the gastric antrurn, in gastric carcinomas and surrounding mucosa by immuohistochemistry. PDX1 was frequently expressed in pseudopyloric glands. The frequency of PDX 1 positive reactivity was higher in differentiated type (39/43, 90.7%) than in undifferentiated type carcinomas (33/52, 63.5%). Our study suggested that PDX 1 plays important roles in development of pseudopyloric glands, and that pseudopyloric glands may be associated with gastric carcinogenesis.
4. We investigated expression of SOX2, a SRY-related HMG box protein, by immuohistochemistry. SOX2 was strongly expressed in the foveolar epithelium, the expression being much higher than that in carcinomas. SOX2 expression was higher in the gastric type than the intestinal type of gastric cancers. Over-expression of SOX2 induced the rnRNA expression of MUc5Ac, a specific mucin marker for the gastric type. These findings indicate that SOX2 may play a role in differentiation of the gastric epithelium, and that SOX2 may be involved in gastric carcinogenesis, particularly in the gastric type. Less
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