ACTIVATION OF SIGNAL-TRANSDUCTION KINASES BY TAMOXIFEN

Purpose, To study the signal transduction mechanisms of tamoxifen via the activation of MAPKs, JNK and ERK in order to understand its regula tion of gene expression. Methods. The effects of tamoxifen (TAM) on th e activation of serine/threonine mitogen-activated protein kinase (MAP K, p42/ERK2) and the stress-activated protein kinases (p46 SAPK or c-J un N-terminal kinase, JNK1) were evaluated using a human cervical epit heloid carcinoma HeLa cell line. Results, TAM activated both JNK1 and ERK2 activities in a time- and dose-dependent manner in HeLa cells. Th e activation of JNK1 was enhanced when the cells were pretreated with prooxidant H2O2. Conclusions. These studies show that TAM activates th e signal transduction kinases, JNK1 and ERK2, which may play important roles in the regulation of gene expression by TAM.