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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2008-10-16
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pubmed:abstractText |
The epidermal growth factor receptor (EGFR) is frequently overexpressed in various tumours of epidermal origin and is held responsible for tumourigenicity and tumour persistence. Increased nuclear factor (NF)-kappaB activity has been suggested to be involved in the malignant behaviour of EGFR-overexpressing cells. However, the mechanisms that regulate EGF-induced NF-kappaB activation are still largely unknown. Here we show that EGF can induce NF-kappaB-dependent gene expression independently from IkappaBalpha degradation or p100 processing in EGFR-overexpressing HEK293T cells. Moreover, EGF-induced NF-kappaB activation could be inhibited by overexpression of ABINs, which were previously identified as intracellular inhibitors of tumour necrosis factor, interleukin-1 and lipopolysaccharide-induced NF-kappaB activation. Knockdown of ABIN-1 by RNA interference boosted the NF-kappaB response upon EGF stimulation. The C-terminal ubiquitin-binding domain containing region of ABINs was crucial and sufficient for NF-kappaB inhibition. Adenoviral gene transfer of ABINs reduced constitutive NF-kappaB activity as well as the proliferation of EGFR-overexpressing A431 and DU145 human carcinoma cells. Altogether, these results demonstrate an important role for an ABIN-sensitive non-classical NF-kappaB signalling pathway in the proliferation of EGFR-overexpressing tumour cells, and indicate a potential use for ABIN gene therapy in the treatment of cancer.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p52 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNIP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNIP2 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1476-5594
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6131-40
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pubmed:dateRevised |
2010-9-10
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pubmed:meshHeading |
pubmed-meshheading:18622428-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:18622428-Cell Line, Tumor,
pubmed-meshheading:18622428-Cell Proliferation,
pubmed-meshheading:18622428-Cyclin D1,
pubmed-meshheading:18622428-DNA-Binding Proteins,
pubmed-meshheading:18622428-Epidermal Growth Factor,
pubmed-meshheading:18622428-Gene Therapy,
pubmed-meshheading:18622428-Humans,
pubmed-meshheading:18622428-I-kappa B Proteins,
pubmed-meshheading:18622428-NF-kappa B,
pubmed-meshheading:18622428-NF-kappa B p52 Subunit,
pubmed-meshheading:18622428-Neoplasms,
pubmed-meshheading:18622428-Phosphorylation,
pubmed-meshheading:18622428-Protein Structure, Tertiary,
pubmed-meshheading:18622428-RNA Interference,
pubmed-meshheading:18622428-Receptor, Epidermal Growth Factor,
pubmed-meshheading:18622428-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
ABINs inhibit EGF receptor-mediated NF-kappaB activation and growth of EGF receptor-overexpressing tumour cells.
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pubmed:affiliation |
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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