Molecular aspect of in cell invasion by pituitary adenoma mediated by hypoxia-relating transcription factor
| Project/Area Number |
17591536
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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 |
Cerebral neurosurgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
YOSHIDA Daizo Nippon Medical School, Neurosurgery, Associate Professor (30210701)
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| Co-Investigator(Kenkyū-buntansha) |
TERAMOTO Akira Nippon Medieal School, Graduate School, Professor (60231445)
KYONSONG Kim Nippon Medical School, Neurosurgery, Assistant Professor (30339387)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,760,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cell invasion / discoidin-domain receotor 1 / hypoxia / Matrix metallonroteinase / Pituitary adenoma / zymography / 蛍光免疫染色 / SDF-1 / ELISA / 浸潤 / MMP / RECK / cDNA microarray / siRNA / 3-D invasion assay / リン酸化 / CREB |
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| Research Abstract |
The discoidin domain receptor 1 (DDR1) tyrosine kinases are a family of cell surface receptors that bind to several types of collagen and facilitate cell adhesion that is known association with several cancers. However, no previous study has examined the expression and function of DDR1 in pituitary adenoma. Tissue microarray analysis of DDR1 expression levels in 52 pituitary adenoma tissues revealed that DDR1 expression was significantly related to hormonal background (Kruskal-Wallis test ; p<0.0001). To further elucidate the function of DDR1 in pituitary adenoma, we developed DDR1 over- and under-expressing cell lines using DDR1 clone transfection and siRNA-based DDR1 gene silencing, respectively, in a human pituitary adenoma cell line (HP-75). Real-time RT-PCR and Western blotting confirmed that expression of both DDR1 isoforms (DDRla and DDR1b) was elevated by clone transfection and diminished by siRNA. Matrigel invasion assays revealed that cell invasion was increased in HP-75 cells over-expressing DDR1 and decreased in cells under-expressing DDR1. Consistent with this, zymography revealed that the activation levels of matrix metalloproteinase (MMP)-2 and -9 were increased and decreased in cells over- and under-expressing DDR1, respectively. Examination of in vitro cell adhesion to collagen types I, II, III and IV with respect to MMP-2 and -9 expression revealed that DDR1 regulated cell adhesion to collagen type I, which was responsible for accelerating secretion of MMP-2 and -9 in DDR1 over-expressing cells. Taken together, these results strongly suggest that DDR1 mediates cell invasion-related signaling between collagen type I and MMP-2 and -9 in pituitary adenoma cells.
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Report
(4 results)
Research Products
(25 results)
