Je. Pawlowski et al., NF-kappa B does not modulate sensitivity of renal carcinoma cells to TNF alpha-related apoptosis-inducing ligand (TRAIL), ANTICANC R, 20(6B), 2000, pp. 4243-4255
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.