Linked Life Data

11306514

Source:http://linkedlifedata.com/resource/pubmed/id/11306514

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-4-19
pubmed:abstractText
Mitogen-activated protein kinase (MAPK) signaling was examined in malignant melanoma cells exposed to hypoxia. Here we demonstrate that hypoxia induced a strong activation of the c-Jun NH2-terminal kinase (JNK), also termed stress-activated protein kinase (SAPK), in the melanoma cell line 530 in vitro. Other members of the MAPK family, e.g., extracellular signal-regulated kinase and p38, remained unaffected by the hypoxic stimulus. Activated JNK/SAPK could also be observed in the vicinity of hypoxic tumor areas in melanoma metastases as detected by immunohistochemistry. Functional analysis of JNK/SAPK activation in the melanoma cell line 530 revealed that activation of JNK/SAPK is involved in hypoxia-mediated tumor cell apoptosis. Both a dominant negative mutant of JNK/SAPK (SAPKbeta K-->R) and a dominant negative mutant of the immediate upstream activator of JNK/SAPK, SEK1 (SEK1 K-->R), inhibited hypoxia-induced apoptosis in transient transfection studies. In contrast, overexpression of the wild-type kinases had a slight proapoptotic effect. Inhibition of extracellular signal-regulated kinase and p38 pathways by the chemical inhibitors PD98058 and SB203580, respectively, had no effect on hypoxiainduced apoptosis. Under normoxic conditions, no influence on apoptosis regulation was observed after inhibition of all three MAPK pathways. In contrast to recent findings, JNK/SAPK activation did not correlate with Fas or Fas ligand (FasL) expression, suggesting that the Fas/FasL system is not involved in hypoxia-induced apoptosis in melanoma cells. Taken together, our data demonstrate that hypoxia-induced JNK/SAPK activation appears to play a critical role in apoptosis regulation of melanoma cells in vitro and in vivo, independent of the Fas/FasL system.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
137-45
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11306514-Anoxia, pubmed-meshheading:11306514-Antigens, CD95, pubmed-meshheading:11306514-Apoptosis, pubmed-meshheading:11306514-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11306514-Humans, pubmed-meshheading:11306514-Immunohistochemistry, pubmed-meshheading:11306514-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:11306514-MAP Kinase Kinase 4, pubmed-meshheading:11306514-Melanoma, pubmed-meshheading:11306514-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:11306514-Mitogen-Activated Protein Kinases, pubmed-meshheading:11306514-Necrosis, pubmed-meshheading:11306514-Neoplasm Invasiveness, pubmed-meshheading:11306514-Neovascularization, Pathologic, pubmed-meshheading:11306514-Proto-Oncogene Proteins c-jun, pubmed-meshheading:11306514-RNA, Messenger, pubmed-meshheading:11306514-Transcription, Genetic, pubmed-meshheading:11306514-Transfection, pubmed-meshheading:11306514-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) is critical for hypoxia-induced apoptosis of human malignant melanoma.
pubmed:affiliation
Department of Dermatology and Venereology, University of Rostock, Germany. manfred.kunz@med.uni-rostock.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't