Santibañez Juan F, Hurtado Claudia
Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, INTA, Universidad de Chile, Casilla 138, Santiago 11, Chile.
FEBS Lett. 2005 Nov 21;579(28):6459-64. doi: 10.1016/j.febslet.2005.10.025. Epub 2005 Nov 2.
Efforts have been made to develop a chemoprevention that selectively triggers apoptosis in malignant cancer cells. Here, we demonstrated that a mutated Ha-Ras activity is required in Anisomycin-induced apoptosis in transformed keratinocytes. Anisomycin stimulates JNK activity and apoptosis in oncogenic Ha-Ras positive cells, but not in normal keratinocytes. This effect was demonstrated in stably transfected cells with dominant negative Ha-Ras, that protected transformed cells, and oncogenic Ha-Ras that sensitized non-transformed cells to Anisomycin-induced apoptosis. Lastly, the treatment of cells with inhibitors of the JNK displayed resistance to Anisomycin induced apoptosis. These data suggests that the oncogenic Ha-Ras is important for Anisomycin-induced JNK activation and apoptosis in transformed keratinocytes.
人们一直在努力开发一种化学预防方法，以选择性地触发恶性癌细胞的凋亡。在此，我们证明了在茴香霉素诱导的转化角质形成细胞凋亡中，需要突变的Ha-Ras活性。茴香霉素刺激致癌性Ha-Ras阳性细胞中的JNK活性和凋亡，但不刺激正常角质形成细胞。在用显性负性Ha-Ras稳定转染的细胞中证实了这种效应，显性负性Ha-Ras保护转化细胞，而致癌性Ha-Ras使未转化细胞对茴香霉素诱导的凋亡敏感。最后，用JNK抑制剂处理细胞显示出对茴香霉素诱导的凋亡具有抗性。这些数据表明，致癌性Ha-Ras对于茴香霉素诱导的转化角质形成细胞中的JNK激活和凋亡很重要。
