Abstract
The roles of transient receptor potential (TRP) cation channels in pancreatic tumorigenesis are essentially unknown. Here, we focus on the TRP melastatin-subfamily (TRPM) members. Expression of the thermally regulated transmembrane Ca(2+)-permeable channel TRPM8 is consistently up-regulated in human pancreatic adenocarcinoma cell lines and tissues. TRPM8-deficient pancreatic cancer cells have reduced ability of proliferation and cell cycle progression with elevated levels of cyclin-dependent kinase inhibitors. These results indicate that TRPM8 is aberrantly over-expressed in pancreatic adenocarcinoma and required for cellular proliferation, and they support further investigation of the potential of TRPM8 as a clinical biomarker and therapeutic target in pancreatic adenocarcinoma.
2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Cell Cycle
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Cell Line, Tumor
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Cell Proliferation*
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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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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RNA Interference
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RNA, Messenger / metabolism
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TRPM Cation Channels / genetics
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TRPM Cation Channels / metabolism*
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Transfection
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Up-Regulation
Substances
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Biomarkers, Tumor
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CDKN1A protein, human
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CDKN1B protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Intracellular Signaling Peptides and Proteins
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RNA, Messenger
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TRPM Cation Channels
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TRPM8 protein, human
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Cyclin-Dependent Kinase Inhibitor p27