Source:http://linkedlifedata.com/resource/pubmed/id/11756236
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2001-12-28
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| pubmed:abstractText |
This study examined the role of signal transduction and apoptosis in malignant transformation induced by arsenic. Prior study showed that chronic arsenite exposure (500 nM, > or =18 weeks) induced malignant transformation in rat liver TRL 1215 cells. In the present work, these transformed cells were compared with passage-matched control cells. In addition, TRL 1215 cells were treated subchronically (up to 6 weeks) with arsenic (termed pre-transformed cells) to define events occurring prior to arsenic-induced transformation. Flow cytometry using annexin/FITC revealed that arsenic-induced apoptosis in transformed cells was markedly suppressed in comparison to control or pre-transformed cells. Ro318220, a strong activator of JNK, enhanced arsenite-induced apoptosis in transformed cells. Densitometric analysis of western blots revealed that the ratios of both Bcl-x(L)/Bax and Bcl-2/Bax were significantly increased (>2.5-fold) in arsenic-transformed cells. Transformed, pre-transformed and control cells were treated with arsenic and levels of phosphorylated extracellular signal-regulated kinases, ERK1/2, JNK1/2 and p38 were determined by western blot analysis. The three mitogen-activated protein kinases (MAPKs) were phosphorylated in a dose-dependent fashion in all cell types. However, the levels of phosphorylated JNK1/2 were markedly decreased in the arsenic-transformed cells, whereas in pre-transformed cells the levels of phosphorylated MAPKs remained the same as in control cells. JNK kinase activity was suppressed in transformed cells whereas Ro318220 enhanced this activity. Thus, during arsenic-induced malignant transformation resistance to apoptosis develops, possibly due to perturbation of the JNK pathway.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arsenic,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Ro 31-8220,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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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 | |
| pubmed:issnType |
Print
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| pubmed:volume |
23
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
151-9
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11756236-Animals,
pubmed-meshheading:11756236-Apoptosis,
pubmed-meshheading:11756236-Arsenic,
pubmed-meshheading:11756236-Blotting, Western,
pubmed-meshheading:11756236-Cell Line, Transformed,
pubmed-meshheading:11756236-Cell Transformation, Neoplastic,
pubmed-meshheading:11756236-Drug Resistance,
pubmed-meshheading:11756236-Enzyme Activation,
pubmed-meshheading:11756236-Flow Cytometry,
pubmed-meshheading:11756236-Hepatocytes,
pubmed-meshheading:11756236-In Situ Nick-End Labeling,
pubmed-meshheading:11756236-Indoles,
pubmed-meshheading:11756236-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:11756236-MAP Kinase Kinase 4,
pubmed-meshheading:11756236-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:11756236-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11756236-Phosphorylation,
pubmed-meshheading:11756236-Proto-Oncogene Proteins,
pubmed-meshheading:11756236-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11756236-Rats,
pubmed-meshheading:11756236-Rats, Inbred F344,
pubmed-meshheading:11756236-Signal Transduction,
pubmed-meshheading:11756236-bcl-2-Associated X Protein
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| pubmed:year |
2002
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| pubmed:articleTitle |
Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway.
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| pubmed:affiliation |
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop F0-09, 111 Alexander Drive, Research Triangle Park, NC 27709, USA.
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| pubmed:publicationType |
Journal Article
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