Linked Life Data

16452207

Source:http://linkedlifedata.com/resource/pubmed/id/16452207

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-2
pubmed:abstractText
Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of immortalized melanocytes. Activation of the transcription factor nuclear factor kappaB (NF-kappaB), a TNF-alpha downstream signaling component, is associated with several human illnesses, including cancer, and NF-kappaB controls the expression of multiple genes involved in tumor progression and metastasis. We now document that AEG-1 is a significant positive regulator of NF-kappaB. Enhanced expression of AEG-1 via a replication-incompetent adenovirus (Ad.AEG-1) in HeLa cells markedly increased binding of the transcriptional activator p50/p65 complex of NF-kappaB. The NF-kappaB activation induced by AEG-1 corresponded with degradation of IkappaBalpha and nuclear translocation of p65 that resulted in the induction of NF-kappaB downstream genes. Infection with an adenovirus expressing the mt32IkappaBalpha superrepressor (Ad.IkappaBalpha-mt32), which prevents p65 nuclear translocation, inhibited AEG-1-induced enhanced agar cloning efficiency and increased matrigel invasion of HeLa cells. We also document that TNF-alpha treatment resulted in nuclear translocation of both AEG-1 and p65 wherein these two proteins physically interacted, suggesting a potential mechanism by which AEG-1 could activate NF-kappaB. Our findings suggest that activation of NF-kappaB by AEG-1 could represent a key molecular mechanism by which AEG-1 promotes anchorage-independent growth and invasion, two central features of the neoplastic phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1509-16
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16452207-Adenoviridae, pubmed-meshheading:16452207-Amino Acid Sequence, pubmed-meshheading:16452207-Carrier Proteins, pubmed-meshheading:16452207-Cell Adhesion, pubmed-meshheading:16452207-Cell Adhesion Molecules, pubmed-meshheading:16452207-Cell Growth Processes, pubmed-meshheading:16452207-Disease Progression, pubmed-meshheading:16452207-HeLa Cells, pubmed-meshheading:16452207-Humans, pubmed-meshheading:16452207-I-kappa B Proteins, pubmed-meshheading:16452207-Interleukin-8, pubmed-meshheading:16452207-Membrane Proteins, pubmed-meshheading:16452207-Molecular Sequence Data, pubmed-meshheading:16452207-NF-kappa B, pubmed-meshheading:16452207-NF-kappa B p50 Subunit, pubmed-meshheading:16452207-Protein Binding, pubmed-meshheading:16452207-RNA, Messenger, pubmed-meshheading:16452207-Transcription Factor RelA, pubmed-meshheading:16452207-Transfection, pubmed-meshheading:16452207-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis.
pubmed:affiliation
Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural