Activating enhancer-binding protein-2 alpha induces cyclooxygenase-2 expression and promotes nasopharyngeal carcinoma growth

Activating enhancer-binding protein-2 alpha (AP-2 alpha) regulates the expression of many cancer-related genes. Here, we demonstrated a novel mechanism by which AP-2 alpha up-regulated cyclooxygenase-2 (COX-2) expression to promote the growth of nasopharyngeal carcinomas (NPCs). High expression of AP-2 alpha in NPC cell lines and tumor tissues from NPC patients was detected and significantly correlated with COX2 expression. Overexpression of AP-2 alpha and COX-2 in tumor tissues was associated with advanced tumor stage, clinical progression, and short survival of patients with NPCs. Knockdown of AP-2 alpha by siRNA markedly inhibited COX-2 expression and PGE2 production in NPC cells. Exogenous expression of AP-2 alpha up-regulated COX-2 and PGE2. Knockdown of AP-2 alpha also significantly suppressed cell proliferation in NPC cells in vitro and tumor growth in a NPC xenograft mouse model. Moreover, we found that p300 played an important role in the AP-2 alpha/COX-2 pathway. AP-2 alpha could co-localize and interact with p300 in NPC cells. Overexpression of the p300, but not its histone acetyltransferase (HAT) domain deletion mutant, promoted the acetylation of AP-2 alpha and its binding on the COX-2 promoter, thereby up-regulated COX-2 expression. Our results indicate that AP-2a activates COX-2 expression to promote NPC growth and suggest that the AP-2 alpha/COX-2 signaling is a potential therapeutic target for NPC treatment.