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Ha‐Ras sensitizes transformed mouse skin cells to Anisomycin‐induced apoptosis
Author(s) -
Santibañez Juan F.,
Hurtado Claudia
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.025
Subject(s) - anisomycin , apoptosis , transfection , microbiology and biotechnology , chemistry , cancer research , downregulation and upregulation , cell culture , biology , kinase , biochemistry , gene , genetics
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.