Aurora-A Contributes to Radioresistance by Increasing NF-kappa B DNA Binding

作者：Oh Eun Taex; Byun Mi Sun; Lee Hyemi; Park Moon Tack; Jue Dae Myung; Lee Chang Woo; Lim Byung Uk; Park Heon Joo^*

来源：Radiation Research, 2010, 174(3): 265-273.

DOI：10.1667/RR2017.1

Aurora-A, a serine/threonine kinase that is overexpressed in certain human cancer cell lines, plays an important role in mitotic progression. Aurora-A has also been reported to be involved in the activation of nuclear factor kappa B (NF-kappa B). The purpose of the present study was to identify the role of Aurora-A in the radiation-induced activation pathway of NF-kappa B. Wild-type and Aurora-A knockdown (Aurora-A(KD)) HeLa cells were irradiated with 4 Gy of gamma rays and the EMSA, luciferase reporter gene assay and immunoblot analysis were performed. The siRNA-based gene knockdown and overexpression system was adopted to elucidate the role of Aurora-A in radiation-induced NF-kappa B pathway activation. The clonogenic survival study indicated that Aurora-A(KD) cells and the wild-type cells transfected with Aurora-A siRNA or RelAlp65 siRNA were more radiosensitive than the wild-type cells. In both the wildtype and Aurora-A(KD) cells, radiation caused I kappa B kinase-mediated phosphorylation, degradation of I kappa B alpha and phosphorylation of RelA/p65. The nuclear translocation of RelA/p65 was also similar in the wild-type and Aurora-A(KD) cells. However, RelA/p65-DNA binding was markedly suppressed in Aurora-A(KD) cells compared to that in wild-type cells. It was concluded that Aurora-A enhances the binding of NF-kappa B to DNA, thereby increasing the gene transcription by NF-kappa B and decreasing the radiosensitivity of the cells.

• 出版日期2010-9