Background: The Notch signaling pathway plays a critical role in embryonic development and carcinogenesis. Aberrant Notch signaling has been linked to a wide variety of cancers. Activation of Notch pathway can either suppress or promote tumors depending on the cell type and context. However, the role of the Notch pathway in the pathogenesis and development of esophageal adenocarcinoma (EAC) is poorly understood. Objective: Elucidate the role of NOTCH signaling pathway in EAC. Methodology: In this study, the expression of Notch components in EAC tissues, matched non-tumor esophageal mucosa and normal esophagus tissues, EAC cell lines (FLO-1, JH-EsoAd1, OE19 and OE33) and 3 primary esophageal normal epithelial cells were assessed by quantitative RT- PCR, western blot analysis, immunofluorescence and immunohistochemistry. The effect of blocking as well as ectopic activation of the Notch pathway on the proliferation, colony formation, and gene expression were also characterized. Results: The aberrant activation of Notch signaling was observed in human EAC clinical samples. Expression of most Notch pathway components was elevated in EAC. The expression of activated NOTCH1 also associated with the differentiation grade of EAC. We found that blocking Notch activity by gamma-secretase inhibitors(GSI) affects the proliferation and/or survival of EAC cell lines and human EAC samples ex vivo cultures. In contrast, this effect was not observed in human esophageal epithelial cell line, Het-1A. However, we observed that activation of Notch signaling by NOTCH1icd could promote colony formation in Het-1A cells. Conclusions: Our results showed that Notch signaling promotes the growth and pathogenesis of EAC. Therefore, Notch signaling pathway could be a promising therapeutic target for treatment of human EAC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3336. doi:1538-7445.AM2012-3336