Elucidation of mechanisms of pancreatic oncogenesis and establishment of novel therapy by modulating Notch signaling

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[Background]Although it is reported that Notch signaling is activated in various cancer cells, the role of Notch signaling at early stage of oncogenesis in pancreas.[Aim]To establish novel mouse pancreatic cancer model using green mouse.To investigate the role of Notch signaling on pancreatic oncogenesis.[Results]1)Notch1 was expressed from PanIN-1A to invasive carcinoma.2)Tubular complex was detected in pancreas two weeks after DMBA injection. PanIN-2 lesion was observed in pancreas one month after DMBA injection. Invasive carcinoma occurred more than two months after DMBA injection. Tumor cells were CK-positive, vimentin-negative.3)Smad4 was downregulated in invasive carcinoma. CyclinD1 and p53 were upregulated in invasive carcinoma.4)Notch1 mRNA was upregulated in PanIN lesion and Invasive carcinoma. PDx1 mRNA was upregulated in PanIN lesion and Invasive carcinoma.[Conculusions]We established novel mouse pancreatic cancer model. Notch signaling was upregulated at early stage of oncogenesis. Notch inhibits differentiation in pancreatic cancer cells.