Research of the impact of glucose dependent insurinotropic polypeptide on pancreatogenesis and on panreas cancer development

器官发生和癌发生之间有一些相似之处。本研究以肠促胰岛素家族成员之一的葡萄糖依赖性促胰岛素多肽（glucose-dependent insulinotropic polypeptide，GIP）为研究对象，探讨GIP在胰腺发生和胰腺癌发生中的作用。小鼠胚胎中GIP受体的缺失显示了发育中胰腺中β细胞向α细胞的转变，这意味着GIP对β细胞发育的贡献。在胰腺癌标本中，随着肿瘤从低级别PanIN发展为真正的癌，GIP受体的表达而不是GIP本身的表达减少。此外，GIP受体的表达伴随着胰腺癌中Pdx 1的减少而减少。我们以前报道过Pdx 1是一个不利的预后因素，这些结果表明，GIP通过Pdx 1在胰腺癌发生的初始阶段发展为胰腺癌。

There are several similarities between organogensis and carcinogenesis. In this study, we focused on one of the incretin family, GIP(glucose-dependent insulinotropic polypeptide) and analyzed the role of GIP on pancreatogenesis as well as on carcinogenesis of the panreas. Loss of GIP receptor in mouse embryo shows transition of the beta cell to the alpha cell in the developing pancreas, which implies GIP comittment on beta cell development. In the pancreatic cancer specimen, the expression of GIP receptor but not of GIP itself diminishes as the tumor develops from low grade PanIN to the authentic carcinoma. Moreover, the expression of GIP receptor concomitantly diminishes as the Pdx1 decreases in the pancreatic cancer. We previously reported Pdx1 tp be an unfavorable prognostic factor, and these results suggest that the GIP develops pancreatic cancer through Pdx1 during the initial stage of the pancreas carcrinogenesis.