| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
We have already established a genetically-engineered mouse model containing pancreas epithelium-specific Kras activation and TGF-beta type II receptor knockout. This model develops differentiated pancreatic ductal adenocarcinoma with abundant stroma including marked fibrosis (desmoplasia), which recapitulates histological features of human pancreatic cancer very well. However, this model cannot approach the cell of origin for pancreatic ductal adenocarcinoma because every pancreatic epithelium possesses genetic alterations described above and an entire pancreas is rapidly occupied by the tumor. In this study, by using Tamoxifen-inducible cre-loxP system driven by Nestin promoter, a new mouse model of adult-onset, Nestin-positive cell-specific Kras activation plus TGF-beta type II receptor knockout was established. Nestin is known to be expressed in pancreatic progenitor cells. This mouse developed focal pancreatic ductal adenocarcinoma as well as pre-cancer lesions, which is considered as a closer approximation of human pancreatic carcinogenesis compared with the former models. This study proves that Nestin-positive cells in the adult pancreas can be the cells of origin for pancreatic ductal adenocarcinoma.
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