Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells.
OBJECTIVE
Ionizing radiation (IR) triggers several intracellular signaling cascades that have commonly been regarded as mitogenic, including the Raf-MEK-Erk kinase cascade. In addition to promoting proliferation, activated MEK and Erk may also prevent cell death induced by cytotoxic stimuli. Because Raf, MEK, and Erk are activated by IR in some tumor cell lines, this suggests that IR-induced activation of the kinase cascade may enhance the survival of irradiated cells.


METHODS
IR-induced activation of MEK and Erk was assessed in irradiated UM-SCC-6 cells, a human squamous carcinoma cell line. Activation of MEK and Erk was blocked with the pharmacological inhibitor of MEK activation, PD098059. Clonogenic survival was assessed in irradiated UM-SCC-6 cells that were pretreated with nothing or with the MEK inhibitor.


RESULTS
In UM-SCC-6 cells, IR doses as low as 2 Gy rapidly activated MEK and Erk. Pretreatment of the cells with the pharmacological inhibitor of MEK activation, PD098059, effectively blocked IR-induced activation of MEK and Erk. However, inhibition of the kinase cascade did not affect the clonogenic survival of irradiated cells in either early or delayed-plating experiments.


CONCLUSIONS
Taken together, these results suggest that although MEK and Erk are rapidly activated by IR treatment, these protein kinases do not affect the clonogenic survival of irradiated UM-SCC6 cells.
Bonner
J A
JA
Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Vroman
B T
BT
Christianson
T J
TJ
Karnitz
L M
LM
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy; D002470:Cell Survival / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D009363:Neoplasm Proteins / Q000378:metabolism / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects*; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human