| Project/Area Number |
07457272
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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 |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SHIOZAKI Hitoshi Osaka University Medical School, Associate Professor, 医学部, 助教授 (70144475)
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| Co-Investigator(Kenkyū-buntansha) |
GOFUKU Junji Osaka University Medical School Hospital, Medical Staff, 医学部・附属病院, 医員
DOKI Yuichiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (20291445)
YANO Masahiko Osaka University Medical School, Assistant Professor, 医学部, 助手 (70273646)
INOUE Masatoshi Osaka University Medical School, Assistant Professor, 医学部, 助手 (80232560)
TSUJINAKA Toshimasa Osaka University Medical School, Lecturer, 医学部, 講師 (40188545)
竹市 雅俊 京都大学, 大学院理学研究科, 教授 (00025454)
田村 茂行 大阪大学, 医学部, 助手 (80281129)
丸山 憲太郎 大阪大学, 医学部・附属病院, 医員
岩澤 卓 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | E-cadherin / beta-catenin / occludin / APC / チロシンリン酸化 / E-CD / β-カテニン / α-カテニン / adberence junction / チロシン リン酸化 / ZO-1 / E-Cadherin / (EGFR) / (AMFR) |
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| Research Abstract |
The purpose of this series of study is to elucidate the implication of disorder of E-cadherin and associated protein in cancer invasion and metastasis.
1) The mechanism for reduction of E-cadherin expression. Among cultured cancer cell lines, no disorder was detected in E-cadherin gene. There was a cell line which dose not express E-cadherin protein in spite of the possession of its mRNA.This might suggest the post transcriptional regulation mechanism of E-cadherin protein.
2) Degradation of E-cadherin by proteolysis. We revealed that a degraded form of E-cadherin was produced in cancer tissues, escaped into blood and, in consequence, detected at high level in the serum of cancer patients. Since more than 60% of gastric cancer patients showed high level of serum E-cadherin, its clinical application as a tumor maker is expected. The cancers with high serum E-cadherin had less amount of E-cadherin in cell surface. Thus, degradation by proteases might explain the reduction of E-cadherin in vivo.
3) Regulation of E-cadherin function by beta-catenin. In cancer cell line and tissue, we detected reduction and/or tyrosin phosphorylation of beta-catenin, which resulted in decline of intercellular adhesion. Tyrosin phosphorylation of b-catenin was induced by EGF.
4) Regulation of tight junction formation by E-cadherin. Occludin, a major tight junction protein, was directly associated with ductal formation. Since E-cadherin was indispensable for the expression of occludin, E-cadherin plays as important role in the regulation of differentiation through occludin expression.
5) beta-catenin in the signal transduction of APC.beta-Catenin in cytosol, which is not bound to E-cadherin, was increased in cancerous tissues. It is interesting that cytosolic beta-Catenin was accumulated not only in colorectal cancers but also in esophageal cancers, where the mutation of APC was seldom observed.
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