Baumann H, Morella K K, Campos S P
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
J Biol Chem. 1993 May 15;268(14):10495-500.
In the rat hepatoma (HTC) cell line, transcription of the alpha 1-acid glycoprotein (AGP) gene is prominently stimulated by dexamethasone. Although interleukin (IL)-1 and IL-6 synergistically enhance expression of the AGP gene in liver, they have no detectable effect on this gene in HTC cells. Nevertheless, HTC cells have mRNA encoding the IL-6 receptor subunits and respond to IL-6 by increasing expression of the junB gene. The mRNA for the 80-kDa IL-6 receptors is increased severalfold following dexamethasone treatment. Even with elevated IL-6 receptor expression, no IL-6 regulation of the AGP gene is observed. The lack of response to IL-6 is also found with the transfected AGP gene sequence, suggesting the absence of specific trans-acting factors. Since IL-6 promotes only a minimal stimulation of the CCAAT/enhancer-binding protein beta, HTC cells lack the indirect IL-6 signaling pathway to acute phase plasma protein genes that has been found to be crucial in other hepatoma cell lines. Considering that a similar IL-6 regulation of the junB gene is manifested in HTC cells and normal liver, a separate IL-6 signal-transducing pathway controlling the AGP gene is assumed to be missing in HTC cells.
在大鼠肝癌（HTC）细胞系中，α1-酸性糖蛋白（AGP）基因的转录受到地塞米松的显著刺激。尽管白细胞介素（IL）-1和IL-6可协同增强肝脏中AGP基因的表达，但它们对HTC细胞中的该基因没有可检测到的影响。然而，HTC细胞具有编码IL-6受体亚基的mRNA，并通过增加junB基因的表达来响应IL-6。地塞米松处理后，80 kDa IL-6受体的mRNA增加了几倍。即使IL-6受体表达升高，也未观察到AGP基因受IL-6调控。在转染的AGP基因序列中也发现对IL-6无反应，这表明缺乏特异性反式作用因子。由于IL-6仅对CCAAT/增强子结合蛋白β有最小程度的刺激，HTC细胞缺乏在其他肝癌细胞系中已发现对急性期血浆蛋白基因至关重要的间接IL-6信号通路。鉴于HTC细胞和正常肝脏中junB基因存在类似的IL-6调控，推测HTC细胞中缺少控制AGP基因的独立IL-6信号转导途径。
