Abstract

Abstract Diabetes mellitus and pancreatic cancer have long been considered to be clinically related to each other. Despite the ample epidemiological evidences indicating relevance between two major human diseases, the precise mechanism to link both of these diseases are still unclear. We demonstrated altered beta-catenin and Wnt3a protein expression in pancreas of diabetic mouse in age-dependent manner, which indicates the chronic diabetic condition may contribute to the pancreatic cancer progression of peri-islet region through elevated Wnt signaling. We also identified the altered expression level of Rspondin-1, secreted agonist of Wnt signaling pathway, in in vivo diabetic mouse model, which showed a similar expression pattern of Wnt3a and beta-catenin. Finally we demonstrated the effect of in vitro diabetic condition on Rspondin expression level of mouse pancreatic beta cell(Min6) and pancreatic cancer cell lines(Panc-1, AsPc-1). The expression level of Rspondin-1 was down-regulated in Min6 cells cultured in high glucose condition, whereas up-regulated in pancreatic cancer cells cultured in in vitro diabetic condition, which correlates with in vivo Rspondin-1 expression study. These results provide new insights about the Wnt signaling and related proteins as molecular linkers of chronic diabetes and pancreatic cancer. Citation Format: So Hyun Park, Sol Kim, Min Yeong Choi, Jiwoon Park, Shinae Kang, Hak-Zoo Kim. Rspondin-1 contributes to tumor cell proliferation via Wnt signaling pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3904. doi:10.1158/1538-7445.AM2015-3904

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