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