The potential role of DEK over-expression in the radiation response of head and neck cancer

Abstract

ObjectiveTo determine if DEK over-expression is associated with radiation resistance in HPV positive head and neck cancer cells. MethodsControl 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. ResultsUpon 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 of γ-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). ConclusionThese 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.