Furuya Y, Ohta S, Yasuda K, Ito H
Department of Urology, School of Medicine, Chiba University, Japan.
Anticancer Res. 1997 Jul-Aug;17(4A):2391-4.
In order to examine the relationship between apoptosis of androgen-independent prostatic cancer cells and cell cycle-associated proteins, TSU-pr1 human prostatic cancer cells were chronically exposed in vitro to the calcium ionophore ionomycin to sustain an elevation in their intracellular free calcium concentration. Temporal analysis demonstrated that the death of these cells does not require cell proliferation and involves fragmentation of genomic DNA into nucleosome sized pieces. Morphological analysis demonstrated that this death process is via apoptosis. During the apoptotic process induced by ionomycin, expression of cyclin-dependent kinase inhibitor p27Kip1 increased. Flow cytometric analysis showed that the treatment resulted in a block in G0/G1 of the cell cycle. These results demonstrate that even nonproliferating androgen-independent prostatic cancer cells can be induced to undergo apoptosis if a modest elevation in the intracellular free calcium is sustained for a sufficient time. p27Kip1 protein is a candidate for the cell cycle regulator in ionomycin-treated TSU-pr1 cells.
为了研究雄激素非依赖性前列腺癌细胞凋亡与细胞周期相关蛋白之间的关系，将TSU-pr1人前列腺癌细胞在体外长期暴露于钙离子载体离子霉素，以维持其细胞内游离钙浓度的升高。时间分析表明，这些细胞的死亡不需要细胞增殖，且涉及基因组DNA断裂成核小体大小的片段。形态学分析表明，这种死亡过程是通过凋亡实现的。在离子霉素诱导的凋亡过程中，细胞周期蛋白依赖性激酶抑制剂p27Kip1的表达增加。流式细胞术分析显示，该处理导致细胞周期在G0/G1期阻滞。这些结果表明，即使是不增殖的雄激素非依赖性前列腺癌细胞，如果细胞内游离钙适度升高并持续足够长的时间，也可被诱导发生凋亡。p27Kip1蛋白是离子霉素处理的TSU-pr1细胞中细胞周期调节因子的候选者。
