Asai A, Miyagi Y, Sugiyama A, Nagashima Y, Kanemitsu H, Obinata M, Mishima K, Kuchino Y
Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.
Oncogene. 1994 Aug;9(8):2345-52.
Gene transfection experiments demonstrated that over-expression of the s-myc gene under the control of a human metallothionein promoter induced apoptosis in cells such as rat and human glioma cells. In contrast to c-Myc-mediated apoptosis requiring withdrawal of serum growth factors, s-myc expression induced apoptosis in glioma cells in the presence of 10% fetal calf serum. Whereas, s-Myc-mediated apoptosis was suppressed in proportion to the increase of bcl-2 expression as seen in c-Myc mediated apoptosis. The s-myc gene was expressed in rat embryo cells being committed to differentiate to hypertrophic chondrocytes which undergo programmed cell death. CAT assay demonstrated that in the NH2-terminal region, the s-Myc protein contains a domain structure required for expression of transactivation activity that is approximately six times higher than that of c-Myc. Therefore, these findings strongly suggest that s-Myc may play an important role in transcription regulation of a set of genes whose expression induces programmed cell death in vitro and in vivo.
基因转染实验表明，在人金属硫蛋白启动子控制下的s-myc基因过表达可诱导大鼠和人胶质瘤细胞等细胞发生凋亡。与c-Myc介导的凋亡需要去除血清生长因子不同，s-myc表达在10%胎牛血清存在的情况下诱导胶质瘤细胞凋亡。然而，与c-Myc介导的凋亡一样，s-Myc介导的凋亡与bcl-2表达的增加成比例地受到抑制。s-myc基因在大鼠胚胎细胞中表达，这些细胞正致力于分化为经历程序性细胞死亡的肥大软骨细胞。CAT分析表明，在NH2-末端区域，s-Myc蛋白含有一种反式激活活性表达所需的结构域结构，其活性约为c-Myc的六倍。因此，这些发现强烈表明，s-Myc可能在一组基因的转录调控中起重要作用，这些基因的表达在体外和体内诱导程序性细胞死亡。
