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Oncotarget. 2015 Mar 10;6(7):5005-21.

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

Author information

1
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
2
Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
3
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
4
State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.

Abstract

Activating enhancer-binding protein-2α (AP-2α) regulates the expression of many cancer-related genes. Here, we demonstrated a novel mechanism by which AP-2α up-regulated cyclooxygenase-2 (COX-2) expression to promote the growth of nasopharyngeal carcinomas (NPCs). High expression of AP-2α in NPC cell lines and tumor tissues from NPC patients was detected and significantly correlated with COX-2 expression. Overexpression of AP-2α and COX-2 in tumor tissues was associated with advanced tumor stage, clinical progression, and short survival of patients with NPCs. Knockdown of AP-2α by siRNA markedly inhibited COX-2 expression and PGE2 production in NPC cells. Exogenous expression of AP-2α up-regulated the COX-2 and PGE2. Knockdown of AP-2α 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-2α/COX-2 pathway. AP-2α 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-2α and its binding on the COX-2 promoter, thereby up-regulated COX-2 expression. Our results indicate that AP-2α activates COX-2 expression to promote NPC growth and suggest that the AP-2α/COX-2 signaling is a potential therapeutic target for NPC treatment.

KEYWORDS:

AP-2α; COX-2; nasopharyngeal carcinoma; p300

PMID:
25669978
PMCID:
PMC4467130
DOI:
10.18632/oncotarget.3215
[Indexed for MEDLINE]
Free PMC Article

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