Sa1997 Osteopontin Splice Variant As a Potential Prognostic Marker for Pancreatic Adenocarcinoma

Abstract

both the crypt-villus and cephalo-caudal intestinal axes. In normal mice fed AIN76A, pS6 staining was sporadic and focal along the cephalo-caudal axis in both villus and crypt epithelial cells. When fed NWD1, staining was more localized to villus cells and more homogeneous along the cephalo-caudal axis. A similar pattern was seen at 3 months in AIN76A fed mice when Notch signaling was inactivated. However, at 9 months staining became less intense and diffuse from villus to crypt. The combination of Notch inactivation and feeding NWD1 produced staining in both villus and crypt cells which was continuous along the cephalo-caudal axis, regardless of age. Conclusion: mTOR activation in the intestine is influenced by both dietary and genetic factors, and is heterogeneous among intestinal epithelial cells. Feeding of NWD1 long-term causes sporadic tumors and elevated mTOR signaling. Although inhibition of Notch signaling may decrease the probability of cell autonomous tumor development, long term effects include secretory cell hyperplasia, copious mucin secretion and inflammation, leading to dysplasia and tumor development, especially in mice fed purified diets. Thus, the increase in mTOR signaling with both higher risk diet and inhibition of Notch signaling, may link this pathway to tumorigenesis regardless of etiology.