Galanin Receptor subtypes 2 as therapeutic targets in Head and Neck Squamous cell Carcinoma
| Project/Area Number |
20592027
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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 |
Otorhinolaryngology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ICHIMURA Keiichi 自治医科大学, 医学部, 教授 (00010471)
NISHINO Hiroshi 自治医科大学, 医学部, 准教授 (50245057)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | GALR2 / G蛋白共役受容体 / 癌抑制遺伝子 / 頭頸部癌 / G蛋白共役受 / GALR1 / G蛋白共役受容 |
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| Research Abstract |
Purpose : Galanin and its receptors, GALR1 and GALR2, are known as tumor suppressor and focused as therapeutic targets in head and neck squamous cell carcinoma(HNSCC). Previously, we demonstrated that the function of signaling pathways of GALR1 and GALR2.In HNSCC cells with silenced GALR1 and GALR2, we showed that reexpressed GALR1 suppresseed tumor cell proliferation via the extracellular-regulated protein kinase-1/2(ERK1/2)-mediated effects on the cyclin-dependent kinase inhibitors(CKI) and cyclinD1.On the other hands, in the GALR2-transfected HNSCC cells, galanin suppressed proliferation and induced apoptosis. Galanin stimulation also mediated decreased expression of cyclin D1 and increased expression of the CKI, p27^<Kip1> and p57^<Kip2>. These effects were similar to GALR1, but GALR2 also induced caspase-3-dependent apoptosis, which was confirmed by Annexin-V staining and DNA fragmentation analysis. Thus, we understood the function of GALR1 and GALR2 as tumor suppressor, but the s
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ignaling pathway of GALR2 is still unclear. In this study, we investigated the signaling pathway of GALR2 in HNSCC cells that have mutant p53 and do not express GALR1.Experimental Design : The HNSCC cell line with a splice site mutation causing a 46-bp p53 off-frame deletion, was stably transfected to express GALR2 and examined the expression of phospho-ERK1/2 by immunoblotting. Results : Galanin treatment of the GALR2-transfected cells caused morphologic changes and a marked decrease in cell number that were not observed in the mock transfected cells. In the GALR2-transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2(ERK1/2) and suppresses cell proliferation, not the mock. transected cells. Galanin stimulation also mediated decreased expression of cyclin D1.Pretreatment with the ERK1/2-specific inhibitor U0126 prevented the suppression of cyclin D1 expression. Conclusion : This study shows that reexpressed GALR2 also suppresses tumor cell proliferation via the almost same pathway for GALR1.However, the ERK1/2-specific inhibitor could not prevent the GALR2 mediated apoptosis. This study suggest that GALR2 uses the different signaling pathways to induce apoptosis or cell cycle arrest, but further investigations are need to understand the GALR2 signaling pathway in detail. Less
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Report
(4 results)
Research Products
(6 results)
