Nielsch U, Pine R, Zimmer S G, Babiss L E
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
J Virol. 1992 Apr;66(4):1884-90. doi: 10.1128/JVI.66.4.1884-1890.1992.
Tumorigenesis is a multistep process involving both genetic and epigenetic changes resulting in altered cellular gene expression. While many phenotypic attributes of transformed cells have been described, the cellular genes responsible for these phenotypes are largely unknown. In this study, we show that the interferon-stimulated gene (ISG) ISG15 is expressed in all adenovirus type 5 (Ad5)-transformed rodent cells tested, in an E1A-dependent manner. We find that the level of ISG15 mRNA correlates with the level of the transcription factor ISGF3, which has been postulated to be the transcriptional activator of ISGs. Consistent with the activation of the interferon transduction pathway in Ad5-transformed cells, beta interferon mRNA is expressed in all but the parental untransformed cell line. The level of ISG15 mRNA in Ad5-transformed cells correlated inversely with the ability of these cells to proliferate in soft agar. This appears to have functional significance, since the phenotype of poor growth in agar could be conferred upon a cell line that grows efficiently in soft agar by using conditioned media from cells that grow poorly in soft agar. The same effect could be mimicked by applying rat interferon. We conclude that the degree of activation of the interferon signal transduction pathway explains differences in the transformation phenotypes among Ad5-transformed cell lines.
肿瘤发生是一个多步骤过程，涉及遗传和表观遗传变化，导致细胞基因表达改变。虽然已经描述了转化细胞的许多表型特征，但负责这些表型的细胞基因在很大程度上尚不清楚。在本研究中，我们表明干扰素刺激基因（ISG）ISG15在所有测试的5型腺病毒（Ad5）转化的啮齿动物细胞中以E1A依赖的方式表达。我们发现ISG15 mRNA的水平与转录因子ISGF3的水平相关，ISGF3被认为是ISG的转录激活因子。与Ad5转化细胞中干扰素转导途径的激活一致，除了亲代未转化细胞系外，所有细胞系中均表达β干扰素mRNA。Ad5转化细胞中ISG15 mRNA的水平与这些细胞在软琼脂中增殖的能力呈负相关。这似乎具有功能意义，因为通过使用在软琼脂中生长不良的细胞的条件培养基，可以将琼脂中生长不良的表型赋予在软琼脂中高效生长的细胞系。应用大鼠干扰素可以模拟相同的效果。我们得出结论，干扰素信号转导途径的激活程度解释了Ad5转化细胞系之间转化表型的差异。
