| Project/Area Number |
20590341
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kobe University |
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Principal Investigator |
YOKOZAKI Hiroshi Kobe University, 大学院・医学研究科, 教授 (10200891)
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| Co-Investigator(Kenkyū-buntansha) |
SEMBA Shuho 神戸大学, 大学院・医学研究科, 准教授 (00302092)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 病理学 / 胃癌 / 幹細胞 / Cdx2 / 分化 / 増殖 / 腸上皮化生 / 異時多発胃癌 |
|---|
| Research Abstract |
Introduction of PTEN expression vectors into TMK-1 gastric cancer cell line revealed that wild type PTEN induced the expressions of Cdx2 as well as intestinal type claudins (claudin-3 and -4). Direct binding of Cdx2 to the promoter region of intestinal claudins was confirmed by chromatin immunoprecipitation. Inverse correlation was observed between the expression levels of nuclear PTEN and phosphorylated Akt in human gastric cancer tissues. Cases with negative nuclear PTEN expression had poor prognosis and infrequent intestinal differentiation. These indicated that activity of Cdx2, inducing the differentiation of gastric cancer, requires the active PTEN phosphatase. Introduction of Cdx2 in the CD133 positive SW480 cells induced growth inhibition, morphological change and suppression of tumorigenesis. Microarray analysis showed that CD133 positive cells express higher levels of TGF-β receptors which was reduced by Cdx2 transfection suggesting the higher sensitivity to TGF-β may required for the maintenance of steaminess of the cancer cells. In the three dimensional culture, TGF-β suppressed the tubular elongation or branching with the induction of Snail at the surface of tumor sphere. Enhanced Snail expression induced by TGF-β was confirmed at the tumor budding of invasion front of the colorectal cancer suggesting the close correlation of Snail expression and reacquisition of stemness of cancer cells.
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