PubMed:11107127 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/11107127","sourcedb":"PubMed","sourceid":"11107127","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/11107127","text":"Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression.\nBACKGROUND: Disruption of apoptotic pathways may be involved in tumor formation, regression, and treatment resistance of neuroblastoma (NB). TNF-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell lines.\nPROCEDURE: In this study we analyzed the expression and function of TRAIL, its agonistic and antagonistic receptors, and important intracellular signaling elements in 18 NB cell lines.\nRESULTS: Semiquantitative RT-PCR revealed that TRAIL-R2 and TRAIL-R3 are the main TRAIL-receptors used by NB cells. Sensitivity to TRAIL-induced apoptosis did not correlate with mRNA expression of TRAIL receptors or cFLIP. Surprisingly, caspase-8 and caspase-10 mRNA was detected in only 5 of 18 NB cell lines. Interestingly, only these five NB cell lines were susceptible to TRAIL-induced apoptosis in a time- and dose-dependent manner.\nCONCLUSIONS: Treatment with 5-aza-2'-deoxycytidine restored mRNA expression of caspase-8 and -10 and TRAIL sensitivity of resistant cell lines, suggesting that gene methylation is involved in caspase inactivation. Since many cytotoxic drugs induce caspase-dependent apoptosis, failure to express caspase-8 and/or caspase-10 might be an important mechanism of resistance to chemotherapy in NB.","tracks":[{"project":"PennBioIE","denotations":[{"id":"T1","span":{"begin":41,"end":54},"obj":"protein"},{"id":"T2","span":{"begin":87,"end":96},"obj":"protein"},{"id":"T3","span":{"begin":230,"end":243},"obj":"protein"},{"id":"T4","span":{"begin":245,"end":247},"obj":"protein"},{"id":"T5","span":{"begin":250,"end":253},"obj":"protein"},{"id":"T6","span":{"begin":521,"end":523},"obj":"protein"},{"id":"T7","span":{"begin":583,"end":591},"obj":"protein"},{"id":"T8","span":{"begin":596,"end":604},"obj":"protein"},{"id":"T9","span":{"begin":642,"end":644},"obj":"protein"},{"id":"T10","span":{"begin":752,"end":757},"obj":"protein"},{"id":"T11","span":{"begin":773,"end":782},"obj":"protein"},{"id":"T12","span":{"begin":787,"end":797},"obj":"protein"},{"id":"T13","span":{"begin":832,"end":834},"obj":"protein"},{"id":"T14","span":{"begin":878,"end":880},"obj":"protein"},{"id":"T15","span":{"begin":1053,"end":1060},"obj":"protein"},{"id":"T16","span":{"begin":1067,"end":1070},"obj":"protein"},{"id":"T17","span":{"begin":1166,"end":1173},"obj":"protein"},{"id":"T18","span":{"begin":1222,"end":1229},"obj":"protein"},{"id":"T19","span":{"begin":1270,"end":1279},"obj":"protein"},{"id":"T20","span":{"begin":1287,"end":1297},"obj":"protein"},{"id":"T21","span":{"begin":1363,"end":1365},"obj":"protein"}],"attributes":[{"subj":"T1","pred":"source","obj":"PennBioIE"},{"subj":"T2","pred":"source","obj":"PennBioIE"},{"subj":"T3","pred":"source","obj":"PennBioIE"},{"subj":"T4","pred":"source","obj":"PennBioIE"},{"subj":"T5","pred":"source","obj":"PennBioIE"},{"subj":"T6","pred":"source","obj":"PennBioIE"},{"subj":"T7","pred":"source","obj":"PennBioIE"},{"subj":"T8","pred":"source","obj":"PennBioIE"},{"subj":"T9","pred":"source","obj":"PennBioIE"},{"subj":"T10","pred":"source","obj":"PennBioIE"},{"subj":"T11","pred":"source","obj":"PennBioIE"},{"subj":"T12","pred":"source","obj":"PennBioIE"},{"subj":"T13","pred":"source","obj":"PennBioIE"},{"subj":"T14","pred":"source","obj":"PennBioIE"},{"subj":"T15","pred":"source","obj":"PennBioIE"},{"subj":"T16","pred":"source","obj":"PennBioIE"},{"subj":"T17","pred":"source","obj":"PennBioIE"},{"subj":"T18","pred":"source","obj":"PennBioIE"},{"subj":"T19","pred":"source","obj":"PennBioIE"},{"subj":"T20","pred":"source","obj":"PennBioIE"},{"subj":"T21","pred":"source","obj":"PennBioIE"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":583,"end":591},"obj":"gene:8795"},{"id":"T1","span":{"begin":642,"end":644},"obj":"disease:C0700095"},{"id":"T2","span":{"begin":583,"end":591},"obj":"gene:8795"},{"id":"T3","span":{"begin":642,"end":644},"obj":"disease:C0027819"},{"id":"T4","span":{"begin":596,"end":604},"obj":"gene:8794"},{"id":"T5","span":{"begin":642,"end":644},"obj":"disease:C0700095"},{"id":"T6","span":{"begin":596,"end":604},"obj":"gene:8794"},{"id":"T7","span":{"begin":642,"end":644},"obj":"disease:C0027819"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"},{"subj":"T4","pred":"source","obj":"DisGeNET"},{"subj":"T5","pred":"source","obj":"DisGeNET"},{"subj":"T6","pred":"source","obj":"DisGeNET"},{"subj":"T7","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":108},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":109,"end":120},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":121,"end":249},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":250,"end":350},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":351,"end":361},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":362,"end":535},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":536,"end":544},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":545,"end":651},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":652,"end":758},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":759,"end":846},"obj":"Sentence"},{"id":"TextSentencer_T11","span":{"begin":847,"end":973},"obj":"Sentence"},{"id":"TextSentencer_T12","span":{"begin":974,"end":986},"obj":"Sentence"},{"id":"TextSentencer_T13","span":{"begin":987,"end":1187},"obj":"Sentence"},{"id":"TextSentencer_T14","span":{"begin":1188,"end":1366},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":108},"obj":"Sentence"},{"id":"T2","span":{"begin":109,"end":120},"obj":"Sentence"},{"id":"T3","span":{"begin":121,"end":249},"obj":"Sentence"},{"id":"T4","span":{"begin":250,"end":350},"obj":"Sentence"},{"id":"T5","span":{"begin":351,"end":361},"obj":"Sentence"},{"id":"T6","span":{"begin":362,"end":535},"obj":"Sentence"},{"id":"T7","span":{"begin":536,"end":544},"obj":"Sentence"},{"id":"T8","span":{"begin":545,"end":651},"obj":"Sentence"},{"id":"T9","span":{"begin":652,"end":758},"obj":"Sentence"},{"id":"T10","span":{"begin":759,"end":846},"obj":"Sentence"},{"id":"T11","span":{"begin":847,"end":973},"obj":"Sentence"},{"id":"T12","span":{"begin":974,"end":986},"obj":"Sentence"},{"id":"T13","span":{"begin":987,"end":1187},"obj":"Sentence"},{"id":"T14","span":{"begin":1188,"end":1366},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T11","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T12","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T13","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T14","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"},{"subj":"T12","pred":"source","obj":"sentences"},{"subj":"T13","pred":"source","obj":"sentences"},{"subj":"T14","pred":"source","obj":"sentences"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T87","span":{"begin":14,"end":19},"obj":"gene:8743"},{"id":"T88","span":{"begin":41,"end":54},"obj":"disease:C0027819"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T87","obj":"T88"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T87","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T88","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"11107127-0#14#19#gene8743","span":{"begin":14,"end":19},"obj":"gene8743"},{"id":"11107127-0#41#54#diseaseC0027819","span":{"begin":41,"end":54},"obj":"diseaseC0027819"}],"relations":[{"id":"14#19#gene874341#54#diseaseC0027819","pred":"associated_with","subj":"11107127-0#14#19#gene8743","obj":"11107127-0#41#54#diseaseC0027819"}],"attributes":[{"subj":"11107127-0#14#19#gene8743","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"11107127-0#41#54#diseaseC0027819","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PennBioIE","color":"#98ec93","default":true},{"id":"DisGeNET","color":"#ec93b2"},{"id":"sentences","color":"#93ccec"},{"id":"DisGeNet-2017-sample","color":"#e6ec93"},{"id":"DisGeNET5_gene_disease","color":"#d893ec"}]}]}}