Elucidation of regeneration-mechanisms through notch signaling and establishment of novel stem cell transplantation in pancreas

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[Background]Notch signaling is known to have a crucial role on organogenesis in various organs.Recentry it is reported that Notch signaling is activated in cancer in various organs.But the precise role of Notch signaling on regeneration of pancreatic ductal cells and oncogenesis are still largely unknown.[Aim]To elucidate the role of Notch signaling on regeneration and oncogenesis.[Results]1)Notch1 expression was observed not only in invasive carcinoma but also in PanIn-1Alesion. Very faint expression of Notch1 was observed in normal pancreatic ducts. Notch1 was expressed intensely in tubular complex in tumor flee area.2)Nestin, a marker of progenitor cells was expressed in pancreatic cancer cells.3)Cell growth and Notch1 expression in cancer cells were inhibited by retinoic acid. Nestin expression was also reduced by retinoic acid. In contrast, carbonic anhydrase II and cytokeratin 19 were upregulated.4)Nestin expression was downregulated by Notch inhibitor. In contrast, carbonic anhydrase II and cytokeratin 19 were upregulated by Notch inhibitor.5)MSX was downregulated by Notch signaling inhibition.6)MSX2 promoted cell growth and induced epithelial mesenchymal transition.[Conclusion]It is suggested that Notch regulates malignant potential in pancreatic cancer cells. It is also suggested that Notch could regulate malignant potential through MSX2.