title: Activating enhancer-binding protein-2α induces cyclooxygenase-2 expression and promotes nasopharyngeal carcinoma growth.
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.
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Dingbo
authors: D
authors: Shi
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Xiangsheng
authors: X
authors: Xiao
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Yun
authors: Y
authors: Tian
authors: Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Lijun
authors: L
authors: Qin
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Fangyun
authors: F
authors: Xie
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Rui
authors: R
authors: Sun
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Jingshu
authors: J
authors: Wang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Wenbin
authors: W
authors: Li
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Tianze
authors: T
authors: Liu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Yao
authors: Y
authors: Xiao
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Wendan
authors: W
authors: Yu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Wei
authors: W
authors: Guo
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Yuqing
authors: Y
authors: Xiong
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Huijuan
authors: H
authors: Qiu
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Tiebang
authors: T
authors: Kang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors: Wenlin
authors: W
authors: Huang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Chong
authors: C
authors: Zhao
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors: Wuguo
authors: W
authors: Deng
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050656:Transcription Factor AP-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: AP-2α; COX-2; nasopharyngeal carcinoma; p300