TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling

Molecular Cancer

Research

Ke Shi¹  Wendan Yu²  Wei Guo²  Jingshu Wang³  Yun Tian³  Lingyi Fu³  Wangbing Chen³  Xiangsheng Xiao³  Dingbo Shi³  Tiebang Kang³  Shusen Wang³  Wuguo Deng⁴  Wenlin Huang⁵ 

[1] Department of Geratology, Xiangya Hospital, Central South University, Changsha, China;Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China;State Key Laboratory of Oncology in South China, Colaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, 10060, Guangzhou, China;State Key Laboratory of Oncology in South China, Colaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, 10060, Guangzhou, China;Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China;State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China;State Key Laboratory of Oncology in South China, Colaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, 10060, Guangzhou, China;State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China;

关键词: Lung cancer;    TFAP2B;    ERK;    VEGF;    Caspase;   

DOI  :  10.1186/1476-4598-13-89

 received in 2014-01-03, accepted in 2014-04-14,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundTFAP2B is a member of the AP2 transcription factor family, which orchestrates a variety of cell processes. However, the roles of TFAP2B in regulating carcinogenesis remain largely unknown. Here, we investigated the regulatory effects of TFAP2B on lung adenocarcinomas growth and identified the underlying mechanisms of actions in non-small cell lung cancer (NSCLC) cells.MethodsWe first examined the expression of TFAP2B in lung cancer cell lines and tumor tissues. We also analyzed the prognostic predicting value of TFAP2B in lung adenocarcinomas. Then we investigated the molecular mechanisms by which TFAP2B knockdown or overexpression regulated lung cancer cell growth, angiogenesis and apoptosis, and further confirmed the role of TFAP2B in tumor growth in a lung cancer xenograft mouse model.ResultsTFAP2B was highly expressed in NSCLC cell lines and tumor tissues. Strong TFAP2B expression showed a positive correlation with the poor prognoses of patients with lung adenocarcinomas (P < 0.001). TFAP2B knockdown by siRNA significantly inhibited cell growth and induced apoptosis in NSCLC cells in vitro and in a lung cancer subcutaneous xenograft model, whereas TFAP2B overexpression promoted cell growth. The observed regulation of cell growth was accompanied by the TFAP2B-mediated modulation of the ERK/p38, caspase/cytochrome-c and VEGF/PEDF-dependent signaling pathways in NSCLC cells.ConclusionsThese results indicate that TFAP2B plays a critical role in regulating lung adenocarcinomas growth and could serve as a promising therapeutic target for lung cancer treatment.

【 授权许可】

Unknown   
© Fu et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.