| 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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| 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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