Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.
作者： Yao Xiao , Jingshu Wang , Yu Qin , Yang Xuan , Yunlu Jia
关键词:
摘要: Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown proteomics assay, we identified validated Ku80, a dimer of Ku participating the repair broken DNA double strands, as new binding protein COX-2 gene promoter. Overexpression Ku80 up-regulated promoter activation expression cells. Silencing by siRNA down-regulated inhibited tumor cell growth vitro xenograft mouse model. knockdown suppressed phosphorylation ERK, resulting inactivation MAPK pathway. Moreover, CBP, transcription co-activator, interacted with acetylated to co-regulate CBP increased acetylation, thereby promoting growth. Suppression CBP-specific inhibitor or well Tissue microarray immunohistochemical analysis adenocarcinomas revealed strong positive correlation between levels clinicopathologic variables. was associated poor prognosis patients cancers. We conclude that promotes is potential therapeutic target cancer.
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