Identification of differentiation regulated gene and application to differentiation inducing gene therapy
| Project/Area Number |
14571210
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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 | Kyushu University |
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Principal Investigator |
SHIRABE Ken a university hospital, assistant professor, 大学病院, 講師 (70264025)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Shinji kyushu university, assistant professor, 大学病院, 講師 (30253420)
SHIMADA Mitsuo kyushu university, associate professor, 大学院・医学研究院, 助教授 (10216070)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | Hepatocellular carcinoma / induction of differentiation / spheroid / metastasis-related gene / 転移規定遺伝子 |
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| Research Abstract |
1.Identification of differentiation inducing-related genes
Microarray analysis was performed to examine the gene expression induced by HDAC inhibitor. TSA, and spheroid formation. The expressing OcU3/4 gene was induced and Early Growth Response A gene was suppressed in microarray analysis both TSA and spheroid examination. These results suggested that these genes were associated with induction of differentiation. Furthermore, liver specific function -related gene (C/EBPα), and cell cycle -related gene(cyclin B1. topoisomerase II) were clown regulated in TSA and spheroid group. The transfection of HDAC1 antisense to HCC cell line induced the suppression of cell growth and accelerating the synthesis of albumin. Now, DNA microarray analysis was operating.
2.Identification of metastasis and /or invasion-related genes in hepatoma
We established the metastatic cell lines (lung, lymph node and intraperitonial metastasis), derived from human cholangiocarcinoma. As a result of DNA microarray analysis, compared with parental cell line, we examined the dickkopf-1 and IL-1 beta, as the intraperitoneal metastasisrelated genes. The IL-1 bet.a transfected cell line showed the increased rate of intraperitoneal metastasis significantly. Wnt signal inhibitor, dickkopf-1, was resulted to be intraperitoneal metastasis in patients with intrahepatic cholangiocarcinoma.. Focal adhesion kinase(FAK), reported as cell migration regulating gene, was recognized that venous invasion and the expression of FAN was correlative in clinical samples. The suppression of Grb7, positioned the lower pathway of FAR, using siRNA inhibited invasion of cancer cells in invasion assay.
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Report
(3 results)
Research Products
(3 results)
