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Mod Pathol. 2014 Apr;27(4):580-93. doi: 10.1038/modpathol.2013.154. Epub 2013 Sep 27.

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

Author information

  • 1Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
  • 2School of Interdisciplinary Bioscience and Bio engineering, Pohang University, Pohang, Korea.
  • 3BRI, Korea Institute of Science and Technology, Seoul, Korea.
  • 4Medical Convergence Research Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 5Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
  • 6Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.

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.

PMID:
24072181
[PubMed - indexed for MEDLINE]
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