Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.
Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.
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人乳腺肿瘤细胞系中肿瘤坏死因子表达和耐药性的诱导。
DOI：
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发表时间：
1987
影响因子：
11.1
通讯作者：
D. Kufe
中科院分区：
文献类型：
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作者：
D. Spriggs;K. Imamura;C. Rodríguez;J. Horiguchi;D. Kufe
肿瘤坏死因子是一种多肽细胞因子，对部分但不是全部肿瘤细胞具有细胞毒作用。这种药物的细胞毒作用的抗药性基础尚不清楚。我们研究了人乳腺癌细胞ZR-75-1对肿瘤坏死因子的耐药性。ZR-75-1细胞具有检测不到的肿瘤坏死因子RNA和蛋白质水平。然而，在这些细胞中，重组人肿瘤坏死因子的转录本被瞬时诱导。这种对肿瘤坏死因子RNA的诱导与细胞裂解产物和培养上清液中的肿瘤坏死因子样蛋白的产生有关。当ZR-75-1细胞暴露于更高浓度的肿瘤坏死因子时，对肿瘤坏死因子诱导的细胞毒性产生稳定的抵抗力。肿瘤坏死因子抵抗细胞，命名为ZR-75-1R，持续表达肿瘤坏死因子转录产物和肿瘤坏死因子样蛋白。此外，ZR-75-1R细胞上清液含有可被抗肿瘤坏死因子多克隆抗体消除的细胞毒活性。ZR-75-1R细胞还具有被肿瘤坏死因子样蛋白占据或下调的肿瘤坏死因子受体。这些结果提示：(1)在ZR-75-1细胞中，肿瘤坏死因子可诱导肿瘤坏死因子转录并产生肿瘤坏死因子样蛋白；(2)对肿瘤坏死因子诱导的细胞毒性的抵抗与稳定的肿瘤坏死因子表达有关。
Tumor necrosis factor (TNF) is a polypeptide cytokine that is cytotoxic to some but not all tumor cells. The basis for resistance to the cytotoxic effects of this agent remains unclear. We have studied the development of TNF resistance in human ZR-75-1 breast carcinoma cells. ZR-75-1 cells have undetectable levels of TNF RNA and protein. However, TNF transcripts are transiently induced in these cells by exposure to recombinant human TNF. This induction of TNF RNA is associated with production of TNF-like protein in cell lysates and culture supernatants. Stable resistance to TNF-induced cytotoxicity develops when ZR-75-1 cells are exposed to increased concentrations of TNF. The TNF-resistant cells, designated ZR-75-1R, continuously express TNF transcripts and a TNF-like protein. Furthermore, ZR-75-1R cell supernatants contain cytotoxic activity that is abrogated by polyclonal antibody against TNF. The ZR-75-1R cells also possess TNF receptors that are occupied or down-regulated by the TNF-like protein. These findings thus suggest that (i) TNF induces TNF transcripts and production of a TNF-like protein in ZR-75-1 cells and (ii) resistance to TNF-induced cytotoxicity is associated with stable TNF expression.