Linge C, Gewert D, Rossmann C, Bishop J A, Crowe J S
Biology Division, Wellcome Foundation Ltd., Beckenham, Kent, United Kingdom.
Cancer Res. 1995 Sep 15;55(18):4099-104.
We have examined the ability of melanoma cell lines and normal human melanocytes, which have demonstrable intact IFN genes, to secrete both IFN-alpha and IFN-beta in response to induction with virus. Normal melanocytes were found to secrete both IFN-alpha and IFN-beta after virus induction. In contrast, although all but one of the melanoma lines tested were capable of secreting IFN-beta, none were capable of IFN-alpha secretion. This phenomenon was not due to defects in either translation of IFN-alpha mRNA or secretion of IFN-alpha proteins, since transfection of melanoma lines with a constitutive IFN-alpha 2b expression vector resulted in the secretion of high levels of IFN. On further examination, this inability to express natural IFN-alpha appeared to be due to a defect in activation of the IFN-alpha promoters, since constructs containing the IFN-alpha promotor were completely unresponsive to viral infection in melanoma cells but inducible in melanocytes. These results show that there is a specific disruption of IFN-alpha gene activation rather than IFN-beta in melanoma lines and suggest that this is due to disruption of a trans-acting IFN-alpha gene transcription factor. Disruption of this factor and its consequences may be important in the development of malignant melanoma.
我们检测了具有可证明完整干扰素基因的黑色素瘤细胞系和正常人黑素细胞在病毒诱导下分泌干扰素α和干扰素β的能力。发现正常黑素细胞在病毒诱导后能分泌干扰素α和干扰素β。相比之下，尽管所测试的黑色素瘤细胞系中除一个外其他都能分泌干扰素β，但没有一个能分泌干扰素α。这种现象并非由于干扰素α信使核糖核酸的翻译或干扰素α蛋白的分泌存在缺陷，因为用组成型干扰素α2b表达载体转染黑色素瘤细胞系会导致高水平干扰素的分泌。进一步研究发现，这种无法表达天然干扰素α的情况似乎是由于干扰素α启动子激活存在缺陷，因为含有干扰素α启动子的构建体在黑色素瘤细胞中对病毒感染完全无反应，但在黑素细胞中可诱导。这些结果表明，在黑色素瘤细胞系中存在干扰素α基因激活的特异性破坏而非干扰素β，提示这是由于反式作用的干扰素α基因转录因子的破坏所致。该因子的破坏及其后果可能在恶性黑色素瘤的发生发展中具有重要意义。
