Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas.
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.
Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Minhee
M
Park
School of Interdisciplinary Bioscience and Bio engineering, Pohang University, Pohang, Korea.
Minhyung
M
Kim
School of Interdisciplinary Bioscience and Bio engineering, Pohang University, Pohang, Korea.
Daehee
D
Hwang
Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Misun
M
Park
Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Won Kyu
WK
Kim
Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Sang Kyum
SK
Kim
BRI, Korea Institute of Science and Technology, Seoul, Korea.
Jihye
J
Shin
Medical Convergence Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Eun Sung
ES
Park
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
Chang Moo
CM
Kang
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
Young-Ki
YK
Paik
Departments of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Hoguen
H
Kim
D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016000:Cluster Analysis; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000032:analysis; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011944:Receptors, Androgen / Q000235:genetics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015398:Signal Transduction / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics
C410798:AR protein, human; D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D011944:Receptors, Androgen