1995 Fiscal Year Final Research Report Summary
Regulatory mechanism of cell adhesion by growth factor signaling in human esophageal cancer
| Project/Area Number |
05671062
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka University |
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Principal Investigator |
INOUE Masatoshi Osaka University Medical School, Assistant Professor, 医学部, 助手 (80232560)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Kentaro Osaka University Medical School, Medical Staff, 医学部付属病院, 医員
IWASAWA Takashi Osaka University Medical School, Medical Staff, 医学部付属病院, 医員
TAMURA Shigeyuki Osaka University Medical School, Assistant Professor, 医学部, 助手
SHIOZAKI Hitoshi Osaka University Medical School, Associate Professor, 医学部, 助教授 (70144475)
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| Project Period (FY) |
1993 – 1995
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| Keywords | epidermal growth factor / intercellular adhesion molecules / tyrosine phosphorylation |
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| Research Abstract |
Recently, it has been appeared to be more of interest that cell growth signal and cell adhesion strongly interact each other. We previously reported that, among esophageal cancer patients, lymphnode metastasis is more frequently observed in cancer cells with overexpression of epidermal growth factor receptor (EGFR) than in those without overexpression of EGFR.On the other hand, we found strong negative correlation between the expression of E-cadherin, an intercellular adhesion molecule, and the frequency of lymphonode metastasis in another study. When we compared the expression of these two molecules using surgical specimen of esophageal cancer patients, we recognized the negative correlation among them, that is, decreased expression of E-cadherin was more frequently observed in the tumors with EGFR overexpression. Therefore, we speculated the existence of interaction among E-cadherin and receptor type tyrosine kinase including EGFR,and analyzed whether E-cadherin mediated cell adhesion is affected by the stimulation of growth factor.
The interaction of EGFR and E-cadherin was studied in in vitro experiment using human esophageal cancer cell line which expresses both EGFR and E-cadherin-catenin complex. The decline of cell adhesion was significant upon the stimulation of EGF,showing dispersed colony formation in both two and three dimensional culture. Western blotting of immunocomplex precipitated by E-cadherin antibody revealed that tyrosine phosphorylation of beta-catenin, one of cadherin binding cytoplasmic protein, was induced by the stimulation of EGF.Taken together, we concluded that growth factor receptor with tyrosine kinase activity phosphorylate tyrosine residue of beta-catenin, and in consequence, cell adhesion was surpressed by the dysfunction of E-cadherin adhesion molecule.
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