Activation of signal transduction kinases by tamoxifen.
OBJECTIVE
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.
Duh
J L
JL
Department of Pharmaceutics and Pharmacodynamics College of Pharmacy, University of Illinois, Chicago 60607-7173, USA.
Yu
R
R
Jiao
J J
JJ
Matwyshyn
G A
GA
Li
W
W
Tan
T H
TH
Kong
A N
AN
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases