NF-kappa B does not modulate sensitivity of renal carcinoma cells to TNF alpha-related apoptosis-inducing ligand (TRAIL).
BACKGROUND
Immune cells express TNF-related apoptosis-inducing ligand (TRAIL) and may play an important role in controlling the growth of renal cancer. For this reason we examined the potential cytotoxic and intracellular signaling effects of TRAIL on several renal cancer cell (RCC) lines.


METHODS
Cytotoxicity was determined using an MTS tetrazolium based assay. Death receptor expression was measured by reverse-transcription polymerase chain reaction. Immunoblot analysis was used to measure cFLIP, caspase-8 and phosphorylated JNK and p38. Activation of NF-kappa B was determined by electrophoretic mobility shift assays.


RESULTS
Two RCC lines were highly sensitive to TRAIL-induced cell death, two were of intermediate sensitivity, and two were insensitive. Sensitivity to TRAIL-stimulated apoptosis did not correlate with expression of death receptors, decoy receptors, or expression of the caspase-8-inhibitory protein cFLIP. Neither activation or inhibition of the NF-kappa B signal transduction pathway protected sensitive cells from TRAIL-induced cell death.


CONCLUSIONS
NF-kappa B, although stimulated in these cell lines, does not play a role in the sensitivity of RCC to TRAIL and could play other functions in TRAIL signaling.
Pawlowski
J E
JE
Division of Medical Oncology, School of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Ave., Denver, CO 80262, USA.
Nesterov
A
A
Scheinman
R I
RI
Johnson
T R
TR
Kraft
A S
AS
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008024:Ligands; D048670:MAP Kinase Kinase 4; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
D051017:Apoptosis Regulatory Proteins; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases