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, ChangMoo Kang, Young-Ki Paik, Hoguen Kim

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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 Jan 1

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Pancreatic Neoplasms
Gene Expression
Neoplasms
Epithelial-Mesenchymal Transition
MicroRNAs
Catenins
Androgen Receptors
Pancreatic Ductal Carcinoma
Genes
Neuroendocrine Tumors
Neoplasm Genes
Transcriptome
Cell Differentiation
Exons
Carcinogenesis
Down-Regulation
Western Blotting
Epithelial Cells
Immunohistochemistry
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Park, Minhee ; Kim, Minhyung ; Hwang, Daehee ; Park, Misun ; Kim, Won Kyu ; Kim, Sang Kyum ; Shin, Jihye ; Park, Eun Sung ; Kang, ChangMoo ; Paik, Young-Ki ; Kim, Hoguen. / Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas. In: Modern Pathology. 2014 ; Vol. 27, No. 4. pp. 580-593.
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Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas. / Park, Minhee; Kim, Minhyung; Hwang, Daehee; Park, Misun; Kim, Won Kyu; Kim, Sang Kyum; Shin, Jihye; Park, Eun Sung; Kang, ChangMoo; Paik, Young-Ki; Kim, Hoguen.

In: Modern Pathology, Vol. 27, No. 4, 01.01.2014, p. 580-593.

Research output: Contribution to journalArticle

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AU - Park, Minhee

AU - Kim, Minhyung

AU - Hwang, Daehee

AU - Park, Misun

AU - Kim, Won Kyu

AU - Kim, Sang Kyum

AU - Shin, Jihye

AU - Park, Eun Sung

AU - Kang, ChangMoo

AU - Paik, Young-Ki

AU - Kim, Hoguen

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