Inoue H, Pan J, Hakura A
Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Japan.
J Virol. 1998 Mar;72(3):2532-7. doi: 10.1128/JVI.72.3.2532-2537.1998.
Previously, we isolated a novel gene, drs, which was downregulated by retroviral oncogenes such as v-src and v-K-ras, from a cDNA library of primary rat embryo fibroblasts. Experiments using a temperature-sensitive mutant of the v-src gene indicated that downregulation of drs mRNA was dependent on functional expression of v-Src. In addition, expression of drs mRNA was also reduced by serum stimulation of G0-arrested normal rat fibroblast cells. To clarify the function of the drs gene in cell transformation and proliferation, we introduced drs linked to a potent promoter into a normal rat cell line, F2408, and examined the effect of ectopic expression of exogenous drs on the transformation by the v-src gene and growth properties. Cells expressing exogenous drs gene showed significantly decreased efficiency of transformation by v-src irrespective of functional expression of v-Src kinase, while the growth rate and G1/S progression of the cells were not suppressed by expression of exogenous drs gene, indicating that drs has the ability to suppress v-src transformation without disturbing cell proliferation.
此前，我们从原代大鼠胚胎成纤维细胞的cDNA文库中分离出一个新基因drs，它会被v-src和v-K-ras等逆转录病毒癌基因下调。使用v-src基因的温度敏感突变体进行的实验表明，drs mRNA的下调依赖于v-Src的功能表达。此外，血清刺激G0期停滞的正常大鼠成纤维细胞也会使drs mRNA的表达降低。为了阐明drs基因在细胞转化和增殖中的功能，我们将与强启动子相连的drs导入正常大鼠细胞系F2408，并检测外源drs的异位表达对v-src基因转化及生长特性的影响。表达外源drs基因的细胞显示，无论v-Src激酶的功能表达如何，其被v-src转化的效率均显著降低，而外源drs基因的表达并未抑制细胞的生长速率和G1/S期进程，这表明drs具有抑制v-src转化而不干扰细胞增殖能力。
