| Project/Area Number |
11671232
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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 |
Digestive surgery
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| Research Institution | Kinki University (2000)
Osaka University (1999) |
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Principal Investigator |
INOUE Masatoshi Kinki University, Associate Professor, 医学部・附属病院, 助教授 (80232560)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Masahiko Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (70273646)
SHIOZAKI Hitoshi Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70144475)
土岐 祐一郎 大阪大学, 医学系研究科, 助手 (20291445)
福地 成晃 大阪大学, 医学部・附属病院, 医員
今村 博司 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | gastric cancer / E-cadherin / a-catenin / b-catenin / IQGAP1 / Intercellular adhesion / colorectal cancer / carcinogenesis / a-catenin / b-catenin / Tiam1 |
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| Research Abstract |
We investigated the expression of IQGAP1 in human gastric cancers by immunohistochemistry and western blot upon protein fractionation, especially in comparison with E-cadherin and catenins expression. In the non-cancerous columnar epithelitum of the stomach, IQGAP1 was expressed at the cell-cell boundary. IQGAP 1 was frequently observed diffusely in the cytoplasm in intestinal-type tumors, but was expressed at the cell membrane in diffuse-type tumors, thus showing significant association with tumor differentiation. Interestingly, the membranous expression of IQGAP1 was inversely correlated with that of E-cadherin or α-catenin. These observations were consistent with the western blot results following protein fractionation. IQGAP1 was dominantly expressed in the soluble fraction in differentiated tumors, however, in undifferentiated tumors, it was mostly in the insoluble fraction. In contrast, both E-cadherin and α-catenin were detected only in the insoluble fraction. In addition, IQGAP1 is reported to bind b-catenin, we investigated the expression of IQGAP1 and b-catenin in human colorectal carcinogenesis. IQGAP1 and b-catenin is localized at the cell-cell boundary, but IQGAP1 is located in cytoplasm in differentiated type adenocarcinoma. In cancers which is the overexpression type of b-catenin, IQGAP1 is mostly located in cytoplasm. In the western blot analysis, IQGAP1 expression in soluble fraction is correlated with b-catenin expression in soluble fraction. Thus, subcellular localization of IQGAP1 from the cytoplasm to the cell membrane was concluded to be correlated with E-cadherin dysfunction and tumor dedifferentiation in gastric and colorectal carcinogenesis.
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