Fu Lingyi, Shi Ke, Wang Jingshu, Chen Wangbing, Shi Dingbo, Tian Yun, Guo Wei, Yu Wendan, Xiao Xiangsheng, Kang Tiebang, Wang Shusen, Huang Wenlin, Deng Wuguo
State Key Laboratory of Oncology in South China, Colaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, China.
Mol Cancer. 2014 Apr 26;13:89. doi: 10.1186/1476-4598-13-89.
TFAP2B 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.
We 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.
TFAP2B 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.
These 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.
TFAP2B是AP2转录因子家族的成员，该家族协调多种细胞过程。然而，TFAP2B在调控肿瘤发生中的作用仍 largely未知。在此，我们研究了TFAP2B对肺腺癌生长的调控作用，并确定了其在非小细胞肺癌（NSCLC）细胞中的潜在作用机制。
我们首先检测了TFAP2B在肺癌细胞系和肿瘤组织中的表达。我们还分析了TFAP2B在肺腺癌中的预后预测价值。然后我们研究了TFAP2B敲低或过表达调控肺癌细胞生长、血管生成和凋亡的分子机制，并在肺癌异种移植小鼠模型中进一步证实了TFAP2B在肿瘤生长中的作用。
TFAP2B在NSCLC细胞系和肿瘤组织中高表达。TFAP2B的强表达与肺腺癌患者的不良预后呈正相关（P < 0.001）。通过siRNA敲低TFAP2B在体外和肺癌皮下异种移植模型中均显著抑制NSCLC细胞的生长并诱导其凋亡，而TFAP2B过表达则促进细胞生长。观察到的细胞生长调控伴随着TFAP2B介导的NSCLC细胞中ERK/p38、caspase/细胞色素c和VEGF/PEDF依赖性信号通路的调节。
这些结果表明TFAP2B在调控肺腺癌生长中起关键作用，可作为肺癌治疗的一个有前景的治疗靶点。
