Cancer research (Chicago, Ill.), 2001-02, Vol.61 (4), p.1314-1319
2001
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- Autor(en) / Beteiligte
- Titel
- Resistance to Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) : induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression
- Ist Teil von
- Cancer research (Chicago, Ill.), 2001-02, Vol.61 (4), p.1314-1319
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2001
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Disruption of apoptotic pathways may be involved in tumor formation, regression, and treatment resistance of neuroblastoma (NB). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in cancer cell lines, whereas normal cells are not sensitive to TRAIL-mediated apoptosis. In this study we analyzed the expression and function of TRAIL and its agonistic and antagonistic receptors as well as expression of cellular FLICE-like inhibitory protein and caspase-2, -3, -8, -9, and -10 in 18 NB cell lines. 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 cellular FLICE-like inhibitory protein. Surprisingly, caspase-8 and caspase-10 mRNA expression 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. Treatment with 5-aza-2'-deoxycytidine restored mRNA and protein expression of caspase-8 and TRAIL sensitivity of resistant cell lines, suggesting that gene methylation is involved in caspase inactivation. The TRAIL system seems to be functional in NB cells expressing caspase-8 and/or caspase-10. Because 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445Titel-ID: cdi_proquest_miscellaneous_76959036
- Format
- –
- Schlagworte
- Amino Acid Chloromethyl Ketones - pharmacology, Antineoplastic agents, Apoptosis - drug effects, Apoptosis - physiology, Apoptosis Regulatory Proteins, Azacitidine - analogs & derivatives, Azacitidine - pharmacology, Biological and medical sciences, Caspase 10, Caspase 8, Caspase 9, Caspase Inhibitors, Caspases - biosynthesis, Caspases - metabolism, Cysteine Proteinase Inhibitors - pharmacology, Dose-Response Relationship, Drug, Enzyme Inhibitors - pharmacology, General aspects, GPI-Linked Proteins, Humans, Jurkat Cells - cytology, Jurkat Cells - drug effects, Medical sciences, Membrane Glycoproteins - biosynthesis, Membrane Glycoproteins - pharmacology, Methylation, Neuroblastoma - enzymology, Neuroblastoma - pathology, Pharmacology. Drug treatments, Receptors, TNF-Related Apoptosis-Inducing Ligand, Receptors, Tumor Necrosis Factor - biosynthesis, Receptors, Tumor Necrosis Factor, Member 10c, Reverse Transcriptase Polymerase Chain Reaction, TNF-Related Apoptosis-Inducing Ligand, TRAIL protein, Tumor Necrosis Factor Decoy Receptors, Tumor Necrosis Factor-alpha - biosynthesis, Tumor Necrosis Factor-alpha - pharmacology