AP-2α downregulation by cigarette smoke condensate is counteracted by p53 in human lung cancer cells

Meng,Xiangjun; Meng,Cuida; Yang,Bing; Zhao,Li; Sun,Xuefei; Su,Yun; Liu,Hongyang; Fan,Feiyue; Liu,Xiaodong; Jia,Lili

doi:10.3892/ijmm.2014.1857

AP-2α downregulation by cigarette smoke condensate is counteracted by p53 in human lung cancer cells

Authors:
- Xiangjun Meng
- Cuida Meng
- Bing Yang
- Li Zhao
- Xuefei Sun
- Yun Su
- Hongyang Liu
- Feiyue Fan
- Xiaodong Liu
- Lili Jia
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Affiliations: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Department of Cell Biology, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Emergency, China-Japan Union Hospital, Changchun, Jilin 130021, P.R. China, Department of Orthopedics, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning 116001, P.R. China, Department of Radiation Hazard Evaluation, Institute of Radiation Medicine of Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, P.R. China
Published online on: July 17, 2014 https://doi.org/10.3892/ijmm.2014.1857
Pages: 1094-1100

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Abstract

Cumulative findings have demonstrated that the dysregulation of tumor suppressor genes may be implicated in cigarette smoke-induced carcinogenesis. Activating enhancer-binding protein 2 (AP-2) is a eukaryotic transcriptional factor that plays a significant role in embryonic development and tumorigenesis. The vertebrate AP-2 family consists of AP-2α, AP-2β, AP-2γ, AP-2δ and AP-2ε. Previous studies have suggested that cigarette smoking disrupts AP-2 regulation. In the present study, we investigated the effects of cigarette smoke condensate (CSC) on AP-2α expression in human lung cancer cell lines (NCI-H1299, NCI-H446 and A549), as well as the potential mechanisms involved. Using RT-qPCR, we found that CSC decreased AP-2α expression by suppressing its transcription in human lung cancer cell lines, particularly in p53-deficient NCI-H1299 cells. Western blotting and luciferase assays were implemented and we found that the restoration of p53 expression rescued the NCI-H1299 cells from CSC-induced AP-2α loss, while the silencing of p53 resulted in increased AP-2α loss induced by CSC, suggesting an antagonizing role of p53 in the regulation of AP-2α by CSC. Our results indicate that AP-2α downregulation may be involved in smoke-induced lung carcinogenesis.

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