2006 Fiscal Year Final Research Report Summary
The expression of Angiopoietin and Tie receptor in colorectal cancer and its roles in proliferation and invasion
Project/Area Number |
17590351
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Nagasaki University |
Principal Investigator |
NAKAYAMA Toshiyuki Nagasaki University, Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Tumor and Diagnostic Pathology, Associate Professor, 大学院医歯薬学総合研究科, 准教授 (30284673)
|
Co-Investigator(Kenkyū-buntansha) |
SEKINE Ichiro Nagasaki University, Professor and Chair, 大学院医歯薬学総合研究科, 教授 (60039922)
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Project Period (FY) |
2005 – 2006
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Keywords | Colorectal cancer / Angiopoietin / Tie / Invasion / Differentiation |
Research Abstract |
There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many types of tyrosine kinase receptors have been reported, among which Tie-1 and 2 constitute a major class. Angiopoietin (Ang)-1 is known to be a ligand of the Tie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and 2 and Ang-1, 2 and 4 expression profile in colorectal adenocarcinoma cells. To elucidate the involvement of Tie-1 and 2 and Ang-1, 2 and 4 in human colorectal adenocarcinomas, we examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and molecular techniques. Among the 96 cases of adenocarcinoma, 87 (90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76 cases (79.2%) showed positive staining in the cytoplasm of the carcinoma cells for the Tie-1 and 2, and Ang-1, 2 and 4 proteins, respectively. Histologically, the expression of Ties and Angs was variable. Tie and Ang expression patterns were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ang-1 and 2 proteins upregulated the tumor cell growth and the invasive activity. And it showed the deformation of tumor cell with the treatment of Ang-1 and 2. Ang-1 and 2 showed upregulated the MAPKinase and PI3Kinase pathways in tumor cells by western blot analyses. However, experiment is still going on. Ties and Angs are highly expressed in human colorectal adenocarcinoma cells and correlated with histological differentiation, tumor progression in colorectal cancer. And the cell signaling pathway was upregulated by the treatment of Ang-1 and 2. These findings suggest that the Tie-Ang receptor-ligand complex is involved in the cellular differentiation and progression of human colorectal adenocarcinoma.
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Research Products
(2 results)