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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
The bile acid deoxycholic acid (DCA) is a known tumor promoter and it has been suggested that DCA-induced apoptosis plays an important role in colon tumor development. In this study we have characterized the capacity of DCA to stimulate mitogen-activated protein kinase (MAPK) activity and examined the effect that MAPK activity had on DCA-induced apoptosis. Analysis of MAPK activity in DCA-treated HCT116 cells using phosphorylation-specific antibodies and in vitro kinase assays indicated that both the extracellular signal-regulated kinase (ERK) and p38 MAPK (p38), but not the c-Jun N-terminal kinase (JNK), were activated. Using pharmacological inhibitors we determined that only ERK could influence DCA cytotoxicity and that elevated ERK activity could suppress DCA-induced apoptosis. This observation was confirmed genetically. Suppressing ERK activity by overexpressing a dominant negative form of the ERK MAP kinase resulted in increased sensitivity to DCA-induced apoptosis whereas elevated ERK activity artificially produced by overexpression of the wild-type ERK kinase blunted DCA-induced apoptosis. Taken together, our results suggest that DCA can stimulate pro-apoptotic and anti-apoptotic signaling pathways and that sensitivity to DCA-induced apoptosis can be modulated by the ERK MAP kinase.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0143-3334
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11159738-Apoptosis,
pubmed-meshheading:11159738-Colonic Neoplasms,
pubmed-meshheading:11159738-Deoxycholic Acid,
pubmed-meshheading:11159738-Down-Regulation,
pubmed-meshheading:11159738-Enzyme Activation,
pubmed-meshheading:11159738-Enzyme Inhibitors,
pubmed-meshheading:11159738-Flavonoids,
pubmed-meshheading:11159738-Humans,
pubmed-meshheading:11159738-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11159738-MAP Kinase Kinase 4,
pubmed-meshheading:11159738-MAP Kinase Signaling System,
pubmed-meshheading:11159738-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:11159738-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:11159738-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11159738-Phosphorylation,
pubmed-meshheading:11159738-Transfection,
pubmed-meshheading:11159738-Tumor Cells, Cultured,
pubmed-meshheading:11159738-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2001
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pubmed:articleTitle |
Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis.
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pubmed:affiliation |
Arizona Cancer Center, Department of Radiation Oncology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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