Abstract
The objective of this study was to explore the pathophysiological relevance of WISP-2/CCN5 in progression of human pancreatic adenocarcinoma (PAC). We found WISP-2/CCN5 mRNA and protein expression was faint and sporadic in PAC and detected in only 8.7-20% of the samples with varying grades as compared to adjacent normal and chronic pancreatitis samples where expression was very high in the ducts and acini. Colocalization studies in tissue-microarray slides revealed WISP-2/CCN5 mRNA loss was associated with p53 overexpression in PAC. Like tissue samples, p53 mutant-PAC cell lines show loss of WISP-2/CCN5. Moreover, functional analysis studies demonstrate exposure of pancreatic cancer cells to WISP-2/CCN5 recombinant protein enhances mesenchymal-epithelial-transition (MET). Collectively, we suggest WISP-2/CCN5 silencing may be a critical event during differentiation and progression of PAC and mutant p53 is possibly an important player in pursuing this episode.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Blotting, Northern
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Blotting, Western
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CCN Intercellular Signaling Proteins
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Differentiation / physiology
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Cell Line, Tumor
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Disease Progression
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Epithelium / metabolism
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Epithelium / pathology
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Immunohistochemistry
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In Situ Hybridization
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Intercellular Signaling Peptides and Proteins / genetics*
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Intercellular Signaling Peptides and Proteins / metabolism
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Mesoderm / metabolism
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Mesoderm / pathology
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Pancreas / chemistry
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Pancreas / metabolism
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Pancreas / pathology
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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Pancreatitis, Chronic / genetics
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Pancreatitis, Chronic / metabolism
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Pancreatitis, Chronic / pathology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Repressor Proteins
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Signal Transduction / genetics*
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Signal Transduction / physiology
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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CCN Intercellular Signaling Proteins
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CCN5 protein, human
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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Recombinant Proteins
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Repressor Proteins
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Transcription Factors
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Tumor Suppressor Protein p53