title: AP-2α downregulation by cigarette smoke condensate is counteracted by p53 in human lung cancer cells.
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.
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Xiangjun
authors: X
authors: Meng
authors: Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors: Cuida
authors: C
authors: Meng
authors: Department of Cell Biology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Bing
authors: B
authors: Yang
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Li
authors: L
authors: Zhao
authors: Department of Emergency, China-Japan Union Hospital, Changchun, Jilin 130021, P.R. China.
authors: Xuefei
authors: X
authors: Sun
authors: Department of Orthopedics, Affiliated Zhongshan Hospital, Dalian University, Dalian, Liaoning 116001, P.R. China.
authors: Yun
authors: Y
authors: Su
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Hongyang
authors: H
authors: Liu
authors: 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.
authors: Feiyue
authors: F
authors: Fan
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Xiaodong
authors: X
authors: Liu
authors: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Lili
authors: L
authors: Jia
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013347:Subcellular Fractions / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D050656:Transcription Factor AP-2; D016159:Tumor Suppressor Protein p53