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首页> 外文期刊>Molecular and Cellular Biology >The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1.
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The mitogenic response to tumor necrosis factor alpha requires c-Jun/AP-1.

机译：对肿瘤坏死因子α的促有丝分裂反应需要c-Jun / AP-1。

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In the present study, we addressed the role of the c-jun proto-oncogene in the mitogenic response of human fibroblasts and primary acute myelogenous leukemia blasts to tumor necrosis factor alpha (TNF-alpha). Our data indicate that TNF-alpha treatment of these cells is associated with transcriptional activation of c-jun, resulting in accumulation of c-jun mRNA and protein expression. In order to elucidate the role of c-Jun/AP-1 in TNF-mediated growth stimulation, the antisense (AS) technique was used. Uptake studies of oligonucleotides were performed with fibroblasts, demonstrating that incorporation of oligomers was maximal at 4 h. Oligodeoxynucleotides remained stable in these cells for up to 24 h. Treatment of fibroblasts with the AS oligonucleotide resulted in intracellular duplex formation followed by an efficient translation blockade of c-Jun/AP-1. In contrast, sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular duplexes and also did not interfere with translation of c-Jun/AP-1, suggesting specific elimination of c-Jun/AP-1 by the AS oligomer. Fibroblasts cultured in the presence of the AS oligonucleotide but not those cultured in the presence of the S or NS oligonucleotide failed to respond proliferatively to TNF-alpha. These findings could be confirmed by experiments with primary acute myelogenous leukemia blasts, which also demonstrated that TNF-induced growth stimulation required c-Jun/AP-1 function. Taken together, our results indicate that activation of c-Jun/AP-1 plays a pivotal role in the signaling cascade initiated by TNF, which leads to a proliferative response of its target cells.
机译：在本研究中，我们探讨了c-jun原癌基因在人成纤维细胞和原发性急性髓性白血病母细胞对肿瘤坏死因子α（TNF-alpha）的促有丝分裂反应中的作用。我们的数据表明，这些细胞的TNF-α处理与c-jun的转录激活有关，导致c-jun mRNA和蛋白质表达的积累。为了阐明c-Jun / AP-1在TNF介导的生长刺激中的作用，使用了反义（AS）技术。用成纤维细胞进行寡核苷酸的摄取研究，表明寡聚体的掺入在4 h达到最大。寡脱氧核苷酸在这些细胞中保持稳定长达24小时。用AS寡核苷酸处理成纤维细胞会导致细胞内双链体形成，然后有效翻译c-Jun / AP-1。相反，有义（S）和无义（NS）寡脱氧核苷酸不能形成细胞内双链体，并且也不会干扰c-Jun / AP-1的翻译，这表明AS低聚物可以特异性消除c-Jun / AP-1。在AS寡核苷酸存在下培养的成纤维细胞，而不在S或NS寡核苷酸存在下培养的成纤维细胞不能对TNF-α增殖反应。这些发现可以通过对原发性急性骨髓性白血病母细胞的实验来证实，该实验还证明了TNF诱导的生长刺激需要c-Jun / AP-1功能。综上所述，我们的结果表明c-Jun / AP-1的激活在TNF引发的信号级联反应中起着关键作用，从而导致其靶细胞的增殖反应。

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