Objective:To determine if DEK over-expression is associated with radiation resistance in HPV positive head and neck cancer cells.Methods:Control and DEK over-expressing keratinocytes and an HPV positive head and neck ...Objective:To determine if DEK over-expression is associated with radiation resistance in HPV positive head and neck cancer cells.Methods:Control and DEK over-expressing keratinocytes and an HPV positive head and neck cancer cell line respectively were irradiated with 2–10 Gy and the impact on cell survival,γ-H2AX(a marker of DNA damage)and RAD51(homologous recombination)were analyzed via clonogenic assays,and immunofluorescence measurements respectively.Results:Upon exposure to increasing doses of radiation,DEK over-expression in keratinocytes at 2,4(P<0.05,P<0.05),and 10 Gy(P<0.01)and an HPV positive head and neck cancer cell line at 2,4,8,and 10 Gy(P<0.01)led to improved clonogenic cell survival.In parallel,irradiation decreased the percent ofγ-H2AX foci at 6,24,and 48 h post-irradiation(P<0.05,P<0.05,and P<0.01 respectively)in NIKS,and at 0,6,24,48 h post-irradiation(P<0.05,P<0.05,P<0.01,P<0.01)in C-SCC1 cells but enhanced the percent of RAD51 foci in both DEK over-expressing cell lines relative to their respective control cells at all times points(P<0.01).Conclusion:These results suggest DEK over-expression contributes to radio-resistance in HPV positive head and neck cancer cells,potentially by improving repair of DNA double strand breaks through homologous recombination.The molecular mechanisms and relevance to in vivo responses needs further investigation.展开更多
基金This work was supported by the National Cancer Institute at the National Institutes of Health K12 Grant(#K12CA133250).
文摘Objective:To determine if DEK over-expression is associated with radiation resistance in HPV positive head and neck cancer cells.Methods:Control and DEK over-expressing keratinocytes and an HPV positive head and neck cancer cell line respectively were irradiated with 2–10 Gy and the impact on cell survival,γ-H2AX(a marker of DNA damage)and RAD51(homologous recombination)were analyzed via clonogenic assays,and immunofluorescence measurements respectively.Results:Upon exposure to increasing doses of radiation,DEK over-expression in keratinocytes at 2,4(P<0.05,P<0.05),and 10 Gy(P<0.01)and an HPV positive head and neck cancer cell line at 2,4,8,and 10 Gy(P<0.01)led to improved clonogenic cell survival.In parallel,irradiation decreased the percent ofγ-H2AX foci at 6,24,and 48 h post-irradiation(P<0.05,P<0.05,and P<0.01 respectively)in NIKS,and at 0,6,24,48 h post-irradiation(P<0.05,P<0.05,P<0.01,P<0.01)in C-SCC1 cells but enhanced the percent of RAD51 foci in both DEK over-expressing cell lines relative to their respective control cells at all times points(P<0.01).Conclusion:These results suggest DEK over-expression contributes to radio-resistance in HPV positive head and neck cancer cells,potentially by improving repair of DNA double strand breaks through homologous recombination.The molecular mechanisms and relevance to in vivo responses needs further investigation.
