Ha-Ras sensitizes transformed mouse skin cells to Anisomycin-induced apoptosis.
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.
Santibañez
Juan F
JF
Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, INTA, Universidad de Chile, Casilla 138, Santiago 11, Chile. jfsantib@inta.cl
Hurtado
Claudia
C
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics*; D002461:Cell Line, Transformed; D004789:Enzyme Activation; D011905:Genes, ras / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000166:cytology
D000841:Anisomycin; D048670:MAP Kinase Kinase 4; D015689:Oncogene Protein p21(ras)