Li X, Liu J, Park J K, Hamilton T A, Rayman P, Klein E, Edinger M, Tubbs R, Bukowski R, Finke J
Department of Immunology, Cleveland Clinic Foundation, Ohio 44195.
Cancer Res. 1994 Oct 15;54(20):5424-9.
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.
最近的数据表明，人类肾细胞癌（RCC）患者T细胞反应诱导不佳可能与信号转导通路的改变有关。我们报告称，RCC患者的T细胞在κB基序特异性DNA结合活性方面存在两种改变。第一种改变涉及核提取物中大量κB结合活性的组成性表达，这在电泳迁移率变动分析中观察到。未受刺激的患者T细胞中κB活性的大小与体外激活的正常个体T细胞中观察到的相似。基于使用针对κB/Rel家族蛋白的抗体进行的蛋白质印迹实验，RCC患者T细胞中组成性表达的κB结合活性主要由NF-κB1（p50）亚基组成。这些患者T细胞中κB结合活性的第二个异常是，作为正常NF-κB复合物一部分的Rel同源家族成员RelA在激活后未在细胞核中被诱导。蛋白质印迹分析在T细胞刺激前后的核提取物中均未检测到任何RelA。RCC患者T细胞中κB结合活性的改变可能会损害它们对各种刺激正常反应的能力。
