Source:http://linkedlifedata.com/resource/pubmed/id/17440816
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2007-6-25
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| pubmed:abstractText |
Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) selectively induces apoptosis in transformed cells. Normal cells and certain tumor cells can evade Apo2L/TRAIL induced cell death, but the determinants of Apo2L/TRAIL sensitivity are poorly understood. To better understand the factors that contribute to Apo2L/TRAIL resistance, we characterized two colon carcinoma lines with pronounced differences in Apo2L/TRAIL sensitivity. Colo205 cells are highly sensitive to Apo2L/TRAIL whereas Colo320 cells are unresponsive. Components of the DISC (death inducing signaling complex) could be immunoprecipitated from both cell lines in response to Apo2L/TRAIL. Sensitizing agents including a proteasome inhibitor conferred Apo2L/TRAIL sensitivity in Colo320 cells, indicating that the apoptotic machinery was intact and functional. We specifically suppressed the expression of Bcl-2, FLIP or XIAP in Colo320 cells. Downregulation of either FLIP or XIAP but not Bcl-2 restored sensitivity of Colo320 cells to Apo2L/TRAIL. Moreover, stable knockdown of XIAP expression in Colo320 subcutaneous tumors resulted in suppression of tumor growth and sensitivity to Apo2L/TRAIL in vivo. Our results indicate that only a specific subset of anti-apoptotic proteins can confer resistance to Apo2L/TRAIL in Colo320 cells. Elucidation of the factors that contribute to Apo2L/TRAIL resistance in tumor cells may provide insight into combination therapies with Apo2L/TRAIL in a clinical setting.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Death Domain,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1360-8185
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
12
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1465-78
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| pubmed:dateRevised |
2008-5-14
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| pubmed:meshHeading |
pubmed-meshheading:17440816-Animals,
pubmed-meshheading:17440816-Apoptosis,
pubmed-meshheading:17440816-Apoptosis Regulatory Proteins,
pubmed-meshheading:17440816-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:17440816-Carcinoma,
pubmed-meshheading:17440816-Colonic Neoplasms,
pubmed-meshheading:17440816-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:17440816-Drug Resistance, Neoplasm,
pubmed-meshheading:17440816-Female,
pubmed-meshheading:17440816-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:17440816-Humans,
pubmed-meshheading:17440816-Mice,
pubmed-meshheading:17440816-Mice, SCID,
pubmed-meshheading:17440816-Receptors, Death Domain,
pubmed-meshheading:17440816-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:17440816-Tumor Cells, Cultured,
pubmed-meshheading:17440816-X-Linked Inhibitor of Apoptosis Protein,
pubmed-meshheading:17440816-Xenograft Model Antitumor Assays
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| pubmed:year |
2007
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| pubmed:articleTitle |
Expression of anti-apoptotic factors modulates Apo2L/TRAIL resistance in colon carcinoma cells.
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| pubmed:affiliation |
Department of Oncology, Amgen Inc., 1201 Amgen Ct. West, Seattle, WA 98119, USA.
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| pubmed:publicationType |
Journal Article
|