T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report.
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 kappa B motif-specific DNA-binding activity. The first alteration involves the constitutive expression of substantial kappa B-binding activity in nuclear extracts, which was observed in the electrophoretic mobility shift assay. The magnitude of kappa B 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 kappa B/Rel family proteins, the kappa B-binding activity constitutively expressed in T cells from RCC patients is composed mostly of the NF-kappa B1 (p50) subunit. The second abnormality in kappa B-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-kappa B 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 kappa B-binding activity in T cells from RCC patients may impair their capacity to respond normally to various stimuli.
Li
X
X
Department of Immunology, Cleveland Clinic Foundation, Ohio 44195.
Liu
J
J
Park
J K
JK
Hamilton
T A
TA
Rayman
P
P
Klein
E
E
Edinger
M
M
Tubbs
R
R
Bukowski
R
R
Finke
J
J
D001483:Base Sequence; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D004273:DNA, Neoplasm; D016328:NF-kappa B