Abstract 5110: Activation of Wnt/β-catenin, hedgehog and androgen receptor signaling pathways in solid pseudopapillary neoplasm of pancreas.

Abstract

Abstract Solid pseudopapillary neoplasm (SPN), is an uncommon pancreatic tumor with distinct clinicopathologic features. Mutations in the exon 3 of β-catenin are characteristically identified in SPNs, however little is known about gene and microRNA expression characteristics. To investigate the molecular characteristics of SPNs, we analyzed mRNA and microRNA expression profiles of 14 SPNs and compared their expressions to that of 6 pancreatic ductal adenocarcinomas, 6 endocrine tumors of pancreas, and 5 non-neoplastic pancreas tissues. We demonstrated both mRNA and microRNA expression profiles completely distinguish SPNs to the other pancreatic tumors and non-neoplastic pancreas tissues. We found that Wnt/β-catenin, Hedgehog and androgen receptor signaling pathways are activated in SPNs by analyzing 1,686 genes that showed specific expression changes in SPN. We also found that 7 microRNAs were specifically down-regulated in SPNs, and miR-30a was most closely associated with the up-regulation of the genes belong to the three distinct activated pathways of SPN. We also demonstrated that genes involved in epithelial to mesenchymal transition (EMT) are up-regulated in SPNs than the other type of pancreatic tumors. SPN is characterized by increased expression of mesenchymal markers (N-cadherin, MMP9, Vercican, TIMP1) and decreased expression of epithelial markers (E-cadherin, Desmoplakin, Mucin1, Caveolin). Considering that activated Wnt/β-catenin and Hedgehog pathways are related to the activation of the genes involved in EMT, these activated signaling pathways of SPNs can explain lack of epithelial cell differentiation, and the molecular mechanism of SPN tumorigenesis. Citation Format: Minhee Park, Minhyung Kim, Daehee Hwang, SangKyum Kim, Eunsung Park, Youngki Paik, Jeonhan Park, Hogeun Kim. Activation of Wnt/β-catenin, hedgehog and androgen receptor signaling pathways in solid pseudopapillary neoplasm of pancreas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5110. doi:10.1158/1538-7445.AM2013-5110