Abnormal epithelial-mesenchymal interaction induces disordered HOX gene expression and enhances metastatic capacity
| Project/Area Number |
16390111
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
HAMADA Jun-ichi Hokkaido Univ., Inst.for Genetic Med., Associate Professor, 遺伝子病制御研究所, 助教授 (50192703)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Mitsuhiro Hokkaido Univ., Inst.for Genetic Med., Associate Professor, 遺伝子病制御研究所, 助教授 (10241316)
MORIUCHI Tetsuya Hokkaido Univ., Inst.for Genetic Med., Professor, 遺伝子病制御研究所, 教授 (20174394)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Homeobox / Epithelial-mesenchymal interaction / Hepatocyte growth factor (HGF) / β-catenin / HOXB3 / Transactivation / Invasion and metastasis / E-cadherin |
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| Research Abstract |
Hepatocyte growth factor (HGF) is known as a mediator of epithelial cells and mesenchymal cells during morphogenesis in embryo. HOX genes act as master controller during the morphogenesis. Invasion and metastasis are considered to be a phenomenon caused from abnormal epithelial-mesenchymal interaction by morphogenesis-related factors including HGF. In this study, we aimed to demonstrate the hypothesis : HGF results in enhancement of invasion and metastasis by the altered expression of HOX genes which regulate metastasis-related genes. We obtained the following results. When human pancreatic cancer SUIT-2 cells were treated with HGF, E-cadhein, disappeared from cell membranes and β-catenin translocated from cell membrane to nucleus. Real-time quantitative RT-PCR analysis revealed that HGF increased the expression of only HOXB3 gene of 39 HOX genes. The results from luciferase reporter assays indicated that the complex of β-catenin and TCF/Lef1 transcription factor is bound to promoter region of HOXB3 gene and transactivates the gene. Cell biological studies showed that HGF promoted the cell scattering and motility of SUIT-2 cells. We are now analySing the phenotypical changes of SUIT-2 cells transfected with HOXB3 expression vectors to explore the genes of which expressions are regulated by HOXB3.
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Report
(3 results)
Research Products
(41 results)
