Furuya Y, Isaacs J T, Shimazaki J
Department of Urology, School of Medicine, Chiba University.
Jpn J Cancer Res. 1995 Dec;86(12):1159-65. doi: 10.1111/j.1349-7006.1995.tb03309.x.
Shionogi Carcinoma 115 (SC 115) cells are a cloned cell line derived from androgen-dependent mouse mammary tumor. They can grow in serum-free culture if a physiological level of androgen is present in the medium, but can not proliferate in culture without testosterone. In the present study, the mechanism of cell death in SC 115 cells after androgen withdrawal was examined. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, androgen withdrawal induces programmed cell death (apoptosis) of SC 115 cells in serum-free culture. Northern blot analysis was used to identify a series of genes whose expression per cell is enhanced during the recruitment of cells from a nonproliferative (i.e. G0) state into G1 (i.e.,cyclins D1 and C), from G1 into the S phase of the cell cycle (i.e., cdk2), and during the programmed cell death pathway (i.e. testosterone repressed prostatic message-2 (TRPM-2), transforming growth factor-beta1 (TGF-beta1) and glucose regulated 78 kilodalton protein (GRP-78). Expression of TRPM-2, TGF-beta1, GRP-78, and calmodulin genes increases, but that of cyclins C and D1, and cdk2 genes decreases during programmed cell death of SC 115 cells. These results demonstrate that androgen-dependent SC 115 cells undergo programmed cell death induced by androgen withdrawal, and that this death does not require proliferation or progression into G1 of the proliferative cell cycle. SC 115 cells should be a good model for investigating programmed death of hormone-dependent cancer.
盐野义癌115（SC 115）细胞是一种从雄激素依赖型小鼠乳腺肿瘤衍生而来的克隆细胞系。如果培养基中存在生理水平的雄激素，它们可以在无血清培养中生长，但在没有睾酮的培养中不能增殖。在本研究中，检测了雄激素撤除后SC 115细胞的细胞死亡机制。根据DNA片段化的时间顺序、形态学变化和细胞活力丧失，雄激素撤除诱导无血清培养的SC 115细胞发生程序性细胞死亡（凋亡）。Northern印迹分析用于鉴定一系列基因，这些基因在细胞从非增殖（即G0）状态进入G1（即细胞周期蛋白D1和C）、从G1进入细胞周期的S期（即细胞周期蛋白依赖性激酶2（cdk2））以及程序性细胞死亡途径（即睾酮抑制前列腺信息-2（TRPM-2）、转化生长因子-β1（TGF-β1）和葡萄糖调节78千道尔顿蛋白（GRP-78））过程中，每个细胞的表达都会增强。在SC 115细胞程序性细胞死亡过程中，TRPM-2、TGF-β1、GRP-78和钙调蛋白基因的表达增加，而细胞周期蛋白C和D1以及cdk2基因的表达减少。这些结果表明，雄激素依赖的SC 115细胞会因雄激素撤除而发生程序性细胞死亡，并且这种死亡不需要增殖或进入增殖细胞周期的G1期。SC 115细胞应该是研究激素依赖性癌症程序性死亡的良好模型。
