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Mol Cancer. 2014 Apr 26;13:89. doi: 10.1186/1476-4598-13-89.

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

Author information

1
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. wangshs@sysucc.org.cn.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
24766673
PMCID:
PMC4021500
DOI:
10.1186/1476-4598-13-89
[Indexed for MEDLINE]
Free PMC Article

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