Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas

Minhee Park, Minhyung Kim, Daehee Hwang, Misun Park, Won Kyu Kim, Sang Kyum Kim, Jihye Shin, Eun Sung Park, Chang Moo Kang, Young Ki Paik, Hoguen Kim

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Solid-pseudopapillary neoplasm is an uncommon pancreatic tumor with distinct clinicopathologic features. Solid-pseudopapillary neoplasms are characterized by mutations in exon 3 of CTNNB1. However, little is known about the gene and microRNA expression profiles of solid-pseudopapillary neoplasms. Thus, we sought to characterize solid-pseudopapillary neoplasm-specific gene expression and identify the signaling pathways activated in these tumors. Comparisons of gene expression in solid-pseudopapillary neoplasm to pancreatic ductal carcinomas, neuroendocrine tumors, and non-neoplastic pancreatic tissues identified solid-pseudopapillary neoplasm-specific mRNA and microRNA profiles. By analyzing 1686 (1119 upregulated and 567 downregulated) genes differentially expressed in solid-pseudopapillary neoplasm, we found that the Wnt/β-catenin, Hedgehog, and androgen receptor signaling pathways, as well as genes involved in epithelial mesenchymal transition, are activated in solid-pseudopapillary neoplasms. We validated these results experimentally by assessing the expression of β-catenin, WIF-1, GLI2, androgen receptor, and epithelial-mesenchymal transition-related markers with western blotting and immunohistochemistry. Our analysis also revealed 17 microRNAs, especially the miR-200 family and miR-192/215, closely associated with the upregulated genes associated with the three pathways activated in solid-pseudopapillary neoplasm and epithelial mesenchymal transition. Our results provide insight into the molecular mechanisms underlying solid-pseudopapillary neoplasm tumorigenesis and its characteristic less epithelial cell differentiation than the other common pancreatic tumors.

Original languageEnglish
Pages (from-to)580-593
Number of pages14
JournalModern Pathology
Volume27
Issue number4
DOIs
Publication statusPublished - 2014 Apr

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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