Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth. Oncotarget. 2015 Mar 8; Authors: Xiao Y, Wang J, Qin Y, Xuan Y, Jia Y, Hu W, Yu W, Dai M, Li Z, Yi C, Zhao S, Li M, Du S, Cheng W, Xiao X, Chen Y, Wu T, Meng S, Yuan Y, Liu Q, Huang W, Guo W, Wang S, Deng W Abstract Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Ov...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research