Recent data suggest that the poor induction of a T-cell response to human renal cell carcinoma (RCC) may be related to alterations in signal transduction pathways. We report that T cells from RCC patients have two alterations in κB motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial κB-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of κB activity in unstimulated patient T cells was similar to that observed in T cells from normal individuals that had been activated in vitro. On the basis of Western blotting experiments using antibodies to κB/Rel family proteins, the κB-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-κB1 (p50) subunit. The second abnormality in κB-binding activity in T cells from these patients is that RelA, a member of the Rel homology family which is part of the normal NF-κB complex, was not induced in the nucleus following activation. Western blotting analysis did not detect any RelA in nuclear extracts either before or after stimulation of T cells. The altered κB-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.
This work was supported in part by USPHS Grant CA 56937.