HYPOGLYCEMIA-INDUCED C-JUN PHOSPHORYLATION IS MEDIATED BY C-JUN N-TERMINAL KINASE-1 AND LYN KINASE IN DRUG-RESISTANT HUMAN BREAST-CARCINOMAMCF-7 ADR CELLS/

We studied the signal transduction mechanism that is involved in c-Jun phosphorylation evident after glucose deprivation in MCF-7/ADR cells, Glucose deprivation caused an immediate increase in tyrosine phosphor ylation in MCF-7/ADR cells and specifically activated Lyn kinase, a sr c family tyrosine kinase. In addition, hypoglycemic treatment strongly activated c-Jun N-terminal kinase 1 (JNK1), leading to the phosphoryl ation and activation of c-Jun. Experiments with Lyn antisense oligonuc leotides demonstrated that Lyn kinase activation was responsible for t he activation of JNK1 but not extracellular signal-regulated kinase. W e also observed glucose deprivation-induced Ras activation in MCF-7/AD R cells. These results indicate a possible Ras-dependent signaling pat hway involving Lyn kinase and JNK1, which leads to the glucose depriva tion-induced responses in MCF-7/ADR cells.