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 (TRA IL) and may play an important role in controlling the growth of renal cance r. For this reason we examined the potential cytotoxic and intracellular si gnaling effects of TRAIL on several renal cancer cell (RCC) lines. Methods: Cytotoxicity was determined using an MTS tetrazolium based assay. Death re ceptor expression was measured by reverse-transcription polymerase chain re action. Immunoblot analysis was used to measure cFLIP, caspase-8 and phosph orylated JNK and p38. Activation of NF-kappaB was determined by electrophor etic mobility shift assays Results: Two RCC lines were highly sensitive to TRAIL-induced cell death, two were of intermediate sensitivity, and two wer e insensitive. Sensitivity to TRAIL-stimulated apoptosis did not correlate with expression of death receptors, decoy receptors, or expression of the c aspase-8-inhibitory protein cFLIP. Neither activation or inhibition of the NF-kappaB signal transduction pathway protected sensitive cells from TRAIL- induced cell death. Conclusions: NF-kappaB, although stimulated in these ce ll lines, does not play a role in the sensitivity of RCC to TRAIL and could play other functions in TRAIL signaling.