Ohmori M, Shirasawa S, Furuse M, Okumura K, Sasazuki T
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Cancer Res. 1997 Nov 1;57(21):4714-7.
The activation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) and/or extracellular signal-regulated kinase (ERK) is involved in ceramide-induced apoptosis in certain cells. To examine the relationship between activated Ki-ras-mediated signals and ceramide-induced apoptosis in human colon cancer cells, JNK/SAPK and ERK activity, as initiated by ceramide, was examined in HCT116, which has a mutation of Ki-ras at codon 13, and HCT116-derived clones, HKe-3 and HKh-2, in which activated Ki-ras was disrupted through gene targeting. In HKe-3 and HKh-2, the activity of JNK/SAPK increased significantly within 60 min following C2 ceramide stimulation, and some apoptosis followed. In contrast, C2 ceramide caused a marked apoptosis in HCT116, but activation of JNK/SAPK was not observed. C2 ceramide did not activate ERK in any of the cell lines. These results suggest that activated Ki-ras contributes to the sensitivity of ceramide-induced apoptosis without JNK/SAPK or ERK activation and that other signaling pathways involved in ceramide-induced apoptosis may be present in human colon cancer cells.
c-Jun氨基末端激酶（JNK）/应激激活蛋白激酶（SAPK）和/或细胞外信号调节激酶（ERK）的激活参与了某些细胞中神经酰胺诱导的凋亡过程。为了研究激活的Ki-ras介导的信号与人类结肠癌细胞中神经酰胺诱导的凋亡之间的关系，我们检测了在密码子13处存在Ki-ras突变的HCT116细胞以及通过基因靶向破坏了激活的Ki-ras的HCT116衍生克隆HKe-3和HKh-2中，由神经酰胺引发的JNK/SAPK和ERK活性。在HKe-3和HKh-2细胞中，C2神经酰胺刺激后60分钟内JNK/SAPK活性显著增加，随后出现了一些凋亡现象。相比之下，C2神经酰胺在HCT116细胞中引起了明显的凋亡，但未观察到JNK/SAPK的激活。C2神经酰胺在任何细胞系中均未激活ERK。这些结果表明，激活的Ki-ras在无JNK/SAPK或ERK激活的情况下，有助于提高神经酰胺诱导凋亡的敏感性，并且人类结肠癌细胞中可能存在其他参与神经酰胺诱导凋亡的信号通路。
