Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells

James A. Bonner, Benjamin T. Vroman, Teresa J H Christianson, Larry M Karnitz

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: 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 and Materials: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)921-925
Number of pages5
JournalInternational Journal of Radiation Oncology Biology Physics
Volume42
Issue number4
DOIs
StatePublished - Nov 1 1998

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Mitogen-Activated Protein Kinase Kinases
Ionizing Radiation
ionizing radiation
Squamous Cell Carcinoma
cancer
activation
Survival
cascades
inhibitors
cells
cultured cells
Cell Survival
Phosphotransferases
Pharmacology
plating
death
pretreatment
stimuli
MAP Kinase Kinase Kinases
tumors

Keywords

  • Human squamous cell carcinoma
  • MEK and Erk protein kinases
  • Radiation response

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Ionizing radiation-induced MEK and Erk activation does not enhance survival of irradiated human squamous carcinoma cells. / Bonner, James A.; Vroman, Benjamin T.; Christianson, Teresa J H; Karnitz, Larry M.

In: International Journal of Radiation Oncology Biology Physics, Vol. 42, No. 4, 01.11.1998, p. 921-925.

Research output: Contribution to journalArticle

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N2 - Purpose: 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 and Materials: 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. Conclusion: 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.

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