2003 Fiscal Year Final Research Report Summary
Analysis of carcinogenesis and differentiation by Notch genes in human digestive tract
| Project/Area Number |
14570441
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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 |
Gastroenterology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
IWATANI Akira Tohoku University, Graduate School of Information Sciences, Assistant Professor, 大学院・情報科学研究科, 助手 (30333876)
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| Co-Investigator(Kenkyū-buntansha) |
SEKINE Hitoshi Tohoku University, Hospital, Assistant Professor, 医学部附属病院, 助手 (90241596)
OHARA Shuichi Tohoku University, Health Administration Center, Associate Professor, 保健管理センター, 助教授 (40223929)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Notch genes / upper GI tract / differentiation / Cdx2 / NFkB / gastric culture cells |
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| Research Abstract |
We investigated to reveal the mechanism of carcinogenesis and differentiation by Notch genes, which decide cell fate, and differentiation -related genes such as a homeobox gene Cdx2 in vitro. First we examined 6 gastric cancer cell lines and 2 colon cancer cell lines for four Notch genes (Notchl-4). We found truncated mRNA expression of Notch4 in KATOIII and SW480, which includes ODO10 repeats in intracellular domain. It may be related with the tumorigenesis of human digestive tract.
Next, we paneled the expression level of cdx1, cdx2, sox2 and mucin genes such as muc1, muc2 and muc5ac using RT-PCR. Intestinal metaplasia related gene, Cdx2 expressed weakly only in gastric cancer cell GOIY among them. And also Muc2 expressed weakly parallel to Cdx2 in GOIY. With the stimulation by H.pylori, time course expression of Notch 1, Odx2 and Muc2 were increased in GOIY using RT-PCR and western blot analysis. NfkB signal transduction pathway was also activated at the same time by H.pylori. Some reported that expression of Notch genes was regulated with NfkB. Considered with those reports, Notchi may initiate the differentiation of gastric stem cell and Cdx2 may induce intestinal metaplasia by H.pylori infection.
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