Source:http://linkedlifedata.com/resource/pubmed/id/18204076
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2008-4-2
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pubmed:abstractText |
Although expression of the anti-apoptotic protein Bcl-2-associated athanogene-1 (BAG-1) has been reported as up-regulated in a number of malignancies, we show for the first time that BAG-1 is over-expressed in medium/large-sized colorectal adenomas and carcinomas compared with normal epithelium. To investigate whether expression of BAG-1 is important for colorectal tumour cell survival, microarray analysis was carried out on the HCT116 colorectal carcinoma cell line following transfection with BAG-1 small interfering RNA (siRNA). Analysis identified altered expression of a subset of potential nuclear factor-kappaB (NF-kappaB)-regulated genes. Furthermore, knock down of BAG-1 was shown to inhibit NF-kappaB transcriptional activity. Inhibition of NF-kappaB activity using BAG-1 siRNA or the NF-kappaB inhibitor BAY-117082 suppressed HCT116 cell yield and induced apoptosis; combined treatment had no additive effect, suggesting that the decrease in cell yield associated with knock down of BAG-1 expression is mediated via inhibition of NF-kappaB. Of clinical relevance, BAG-1 siRNA sensitized colorectal carcinoma cells to apoptosis induced by potential therapeutic agent TRAIL as well as tumour necrosis factor-alpha, both inducers of NF-kappaB activity. In summary, knock down of BAG-1 leads to inhibition of NF-kappaB, identifying BAG-1 as a novel regulator of NF-kappaB. It is proposed that, by inhibiting NF-kappaB, suppression of BAG-1 could represent a novel strategy to impede colorectal cancer cell survival and as an adjuvant increase sensitivity to current therapeutic regimes.
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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/BCL2-associated athanogene 1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1460-2180
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
849-57
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pubmed:meshHeading |
pubmed-meshheading:18204076-Adenoma,
pubmed-meshheading:18204076-Carcinoma,
pubmed-meshheading:18204076-Cell Line, Tumor,
pubmed-meshheading:18204076-Cell Survival,
pubmed-meshheading:18204076-Colonic Neoplasms,
pubmed-meshheading:18204076-Colorectal Neoplasms,
pubmed-meshheading:18204076-DNA-Binding Proteins,
pubmed-meshheading:18204076-Disease Progression,
pubmed-meshheading:18204076-Humans,
pubmed-meshheading:18204076-NF-kappa B,
pubmed-meshheading:18204076-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18204076-RNA, Small Interfering,
pubmed-meshheading:18204076-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18204076-Transcription Factors,
pubmed-meshheading:18204076-Transfection,
pubmed-meshheading:18204076-Tumor Cells, Cultured
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pubmed:year |
2008
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pubmed:articleTitle |
BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-kappaB activity.
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pubmed:affiliation |
Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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