prline-rich endogenous antimicrobial peptide suppresses colon carcinoma cell proliferation by adaptor molecule competition
| Project/Area Number |
12670452
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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 | Asahikawa Medical College |
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Principal Investigator |
FUJIMOTO Yoshinori Asahikawa Medical College, Medicine Instructor, 医学部, 助手 (90292127)
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| Co-Investigator(Kenkyū-buntansha) |
KOHGO Yutaka Asahikawa Medical College, Medicine Professor, 医学部, 教授 (10133183)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | antimicrobial peptide / PR-39 / syndecan / actin / signal transduction / colon carcinoma / PI3 Kinase / PI3 Kinase / K-ras |
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| Research Abstract |
PR-39, which is an endogenous antimicrobial peptide, can bind to Src homology 3 domains of the NADPH complex protein p47phox and the signaling adapter protein p130Cas. Recently, we have reported that PR-39, gene transduction altered invasive activity and actin structure on human hepatocellular carcinoma cells, suggesting that this peptide affects cellular signaling pathway due to its proline-rich motif. In order to clarify the mechanism of the PR-39 functions, we transfected with PR-39 gene into mouse NIH3T3 cells which were already transformed with human activated k-ras gene. The PR-39 gene transfectant showed a reorganization of actin structure and suppression of cell proliferation both in vitro and in vivo. Co-immunoprecipitation analysis revealed that the PR-39 binds to PI3-kinase p85a, which is a regulatory subunit of PI3-kinase and one of the effectors by which ras induces cytoskeletal changes and stimulates the mitogenesis. PI3-kinase activity of the PR-39 gene transfectant was decreased compared with that of the ras transformant. These results suggest that the PR-39 alters actin structure and cell proliferation rate by binding to PI3-kinase p85a and suppressing the PI3-kinase activity, The PR-39 gene transfectant derived from colon carcinoma cells also showed the morphological change and the suppression of the proliferation in vitro and vivo, suggesting that PR-39 might be a candidate for the targeting therapy of cancers.
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Report
(3 results)
Research Products
(4 results)
