Seliger B, Hammers S, Höhne A, Zeidler R, Knuth A, Gerharz C D, Huber C
III. Medical Clinic, Department of Hematology/Oncology, Johannes Gutenberg-University, 55101 Mainz, Germany.
Clin Cancer Res. 1997 Apr;3(4):573-8.
Some human tumor cells exhibit deficient expression of the peptide transporters TAP1 and TAP2 and of the proteasome subunits low molecular weight protein (LMP)-2 and LMP-7, which could be partially restored by cytokine treatment. Here, we show that IFN-gamma stimulation of human renal cell carcinoma lines increased the MHC class I, transporter associated with antigen processing (TAP), and LMP transcript and protein levels, but TAP and LMP expression are more rapidly induced by IFN-gamma than MHC class I molecules. No correlation between the level of induction of the MHC class I antigen presentation genes and IFN sensitivity/resistance was detected. The IFN-gamma-mediated increase of MHC class I, TAP-1, and LMP-2 expression was independent of de novo protein synthesis. Analysis of the dual TAP-1/LMP-2 promoter activity revealed that TAP-1 and LMP-2 expression are controlled by IFN-gamma at the transcriptional level. Site-specific mutations in the IFN-gamma-responsive element of the TAP-1/LMP-2 promoter blocked induction by IFN-gamma. Thus, the IFN-gamma-mediated coordinated transcriptional up-regulation of TAP-1 and LMP-2 expression occurs through the use of a common regulatory element, which might result in enhanced recognition of renal cell carcinoma cells by the immune system.
一些人类肿瘤细胞表现出肽转运体TAP1和TAP2以及蛋白酶体亚基低分子量蛋白（LMP）-2和LMP-7的表达缺陷，细胞因子处理可部分恢复这种缺陷。在此，我们表明，用干扰素-γ刺激人肾癌细胞系可增加MHC I类分子、与抗原加工相关的转运体（TAP）以及LMP的转录本和蛋白水平，但与MHC I类分子相比，干扰素-γ诱导TAP和LMP表达的速度更快。未检测到MHC I类抗原呈递基因的诱导水平与干扰素敏感性/抗性之间的相关性。干扰素-γ介导的MHC I类分子、TAP-1和LMP-2表达的增加与从头合成蛋白无关。对双TAP-1/LMP-2启动子活性的分析表明，TAP-1和LMP-2的表达在转录水平上受干扰素-γ的控制。TAP-1/LMP-2启动子的干扰素-γ反应元件中的位点特异性突变可阻断干扰素-γ的诱导作用。因此，干扰素-γ介导的TAP-1和LMP-2表达的协同转录上调是通过使用一个共同的调控元件实现的，这可能导致免疫系统对肾癌细胞的识别增强。
