Identification of molecular targets associated with activation of GPCR signal pathway in pancreatic cancer
Project/Area Number |
24659167
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Human pathology
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Research Institution | Tokyo Women's Medical University |
Principal Investigator |
FURUKAWA Toru 東京女子医科大学, 医学部, 教授 (30282122)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 膵臓がん / シグナル伝達 / GPCR / MAPK / PI3K / 遺伝子発現 / 分子標的 / GNAS / RNA干渉 |
Outline of Final Research Achievements |
We examined phenotypes of pancreatic ductal lineage cells with exogenous expression of either wild-type or mutated (R201H) GNAS. We found that exogenous GNAS upregulated intracellular cAMP and varying altered expression of mucin genes. Exogenous GNAS did not promote cell growth but suppressed it in some of the cells. Global gene expression profiling showed drastic alterations of the gene expression profiles by exogenous mutated GNAS and led to identify downstream genes of activated GPCR pathway. We found interactions between the signaling pathways of GPCR, MAPK, and PI3K on expression of mucin genes. We generated transgenic mice lines with Lox-STOP-Lox (LSL)-GNASR201H under CAG promoter. By crossing this mice line with LSL-KrasG12D mice and Ptf1a-cre mice, we showed that mutated GNAS and Kras cooperatively promoted pancreatic tumorigenesis recapitulating IPMN. This mouse model may serve as a platform to find biomarkers and effective drugs for diseases associated with GNAS mutations.
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Report
(4 results)
Research Products
(17 results)
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[Presentation] A GNAS mutation found in pancreatic intraductal papillary mucinous neoplasms changes mucin gene expression and gene expression profiles.2014
Author(s)
Komatsu H, Sakata N, Aoki T, Motoi F, Naitoh T, Katayose Y, Egawa S, Unno M, Furukawa T.
Organizer
105th Annual Meeting of American Association for Cancer Research
Place of Presentation
San Diego, CA, USA
Year and Date
2014-04-05 – 2014-04-09
Related Report
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