Linked Life Data

18942706

Source:http://linkedlifedata.com/resource/pubmed/id/18942706

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-12-16
pubmed:abstractText
Nuclear factor kappa B (NF-kappaB) signaling is deregulated in many tumor types, resulting in aberrant expression and/or activation of NF-kappaB transcriptional complexes. We have previously reported that nuclear expression of the NF-kappaB subunit p50 is strongly correlated with melanoma progression and poor 5-year patient survival. In this study, we used cDNA microarray to analyze the gene expression profiles of melanoma cells overexpressing NF-kappaB p50. We found that NF-kappaB p50 expression strongly induced interleukin-6 (IL-6) upregulation in melanoma cells at both the transcriptional and translational levels and that IL-6 production by melanoma cells enhanced the growth of endothelial cells in vitro. Expression of activating transcription factor 3 (ATF3), a negative regulator of IL-6 gene transcription, inhibited p50-mediated IL-6 upregulation. Knockdown of p50 expression using lentiviral-based shRNA abrogated IL-6 induction in melanoma cells and inhibited its effects on endothelial cell growth. Finally, we used an in vivo matrigel plug assay to show that NF-kappaB p50 overexpression promotes angiogenesis, while silencing NF-kappaB p50 inhibits blood vessel formation. Our results demonstrate for the first time that the NF-kappaB p50 subunit mediates melanoma angiogenesis by specifically upregulating IL-6, highlighting a novel and important role for the NF-kappaB p50/IL-6 signaling axis in melanoma progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
494-501
pubmed:meshHeading
pubmed-meshheading:18942706-Activating Transcription Factor 3, pubmed-meshheading:18942706-Animals, pubmed-meshheading:18942706-Cell Line, Tumor, pubmed-meshheading:18942706-Cell Proliferation, pubmed-meshheading:18942706-Collagen, pubmed-meshheading:18942706-Drug Combinations, pubmed-meshheading:18942706-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18942706-Humans, pubmed-meshheading:18942706-Interleukin-6, pubmed-meshheading:18942706-Laminin, pubmed-meshheading:18942706-Male, pubmed-meshheading:18942706-Mice, pubmed-meshheading:18942706-Mice, Nude, pubmed-meshheading:18942706-NF-kappa B p50 Subunit, pubmed-meshheading:18942706-Neoplasm Transplantation, pubmed-meshheading:18942706-Neovascularization, Pathologic, pubmed-meshheading:18942706-Proteoglycans, pubmed-meshheading:18942706-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Nuclear factor kappa B subunit p50 promotes melanoma angiogenesis by upregulating interleukin-6 expression.
pubmed:affiliation
Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't