IONIZING RADIATION-INDUCED MEK AND ERK ACTIVATION DOES NOT ENHANCE SURVIVAL OF IRRADIATED HUMAN SQUAMOUS CARCINOMA-CELLS

Purpose: Ionizing radiation (IR) triggers several intracellular signal ing cascades that have commonly been regarded as mitogenic, including the Raf-MEK-Erk kinase cascade,ln addition to promoting proliferation, activated MEK and Erk may also prevent cell death induced by cytotoxi c stimuli. Because Raf, MEK, and Erk are activated by IR in some tumor cell lines, this suggests that IR-induced activation of the kinase ca scade may enhance the survival of irradiated cells. Methods and Materi als: IR-induced activation of MEK and Erk was assessed in irradiated U M-SCC-6 cells, a human squamous carcinoma cell line. Activation of MEK and Erk was blocked with the pharmacological inhibitor of MEK activat ion, PD098059. Clonogenic survival was assessed in irradiated UM-SCC-6 cells that were pretreated with nothing or with the MEK inhibitor. Re sults: In UM-SCC-6 cells, IR doses as low as 2 Gy rapidly activated ME K and Erk. Pretreatment of the cells with the pharmacological inhibito r of MEK activation, PD098059, effectively blocked IR-induced activati on of MEK and Erk. However, inhibition of the kinase cascade did not a ffect the clonogenic survival of irradiated cells in either early or d elayed-plating experiments. Conclusion: Taken together, these results suggest that although MEK and Erk are rapidly activated by IR treatmen t, these protein kinases do not affect the clonogenic survival of irra diated UM-SCC6 cells. (C) 1998 Elsevier Science Inc.