Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Japan; Division of Genome Stability Research, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
FEBS J. 2014 Apr;281(7):1892-900. doi: 10.1111/febs.12752. Epub 2014 Mar 6.
Necrosis and apoptosis are the two major forms of cell death. We have studied the mechanisms that regulate the cell death observed during treatment of mouse cancer cell line FM3A with the anticancer drug 5-fluoro-2'-deoxyuridine (FUdR). To detect causal differences between necrosis and apoptosis, we exploited the necrosis in original clone F28-7 and the apoptosis in its variant F28-7-A that occur on treatment with FUdR. Activating transcription factor 3 (ATF3) was strongly induced during necrosis but not apoptosis. In addition, we found that ATF3 expression is regulated by heat shock protein 90 (HSP90) at the mRNA stage. Knockdown of Atf3 by siRNA in the F28-7 cells resulted in apoptotic morphology rather than necrotic morphology. These results suggest that ATF3 is a cell-death regulator in necrosis and apoptosis.
细胞坏死和细胞凋亡是细胞死亡的两种主要形式。我们研究了在使用抗癌药物 5-氟-2'-脱氧尿苷（FUdR）治疗 FM3A 小鼠癌细胞系时观察到的细胞死亡所涉及的调控机制。为了检测细胞坏死和细胞凋亡之间的因果差异，我们利用了 FUdR 处理时原始克隆 F28-7 中的细胞坏死和其变体 F28-7-A 中的细胞凋亡。在细胞坏死过程中强烈诱导激活转录因子 3（ATF3）的表达，但在细胞凋亡过程中没有。此外，我们发现 ATF3 的表达受热休克蛋白 90（HSP90）在 mRNA 水平上的调控。在 F28-7 细胞中用 siRNA 敲低 Atf3 导致凋亡形态而不是坏死形态。这些结果表明 ATF3 是细胞坏死和细胞凋亡中的细胞死亡调节剂。
