NF-kappa B does not modulate sensitivity of renal carcinoma cells to TNF alpha-related apoptosis-inducing ligand (TRAIL)

J E Pawlowski, A Nesterov, R I Scheinman, T R Johnson, A S Kraft
Anticancer Research 2000, 20 (6): 4243-55

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.

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