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    題名: Cyclooxygenase-2 expression is up-regulated by 2-aminobiphenyl in a ROS and MAPK-dependent signaling pathway in a bladder cancer cell line
    作者: 陳師慶;Chen, Chien-Cheng;Cheng, Yu-Yang;Chen, Ssu-Ching;Tuan, Yen-Fan;Chen, Yun-Ju;Chen, Chien-Yen;Chen, Lei-Chin
    貢獻者: 生醫理工學院生命科學系
    關鍵詞: Aminobiphenyl Compounds - toxicity;Cell Line, Tumor;Cell Survival - drug effects;Cyclooxygenase 2 - genetics;Gene Expression Regulation, Enzymologic - drug effects;Hair Dyes;Humans;MAP Kinase Signaling System - drug effects;NADPH Oxidases - metabolism;Reactive Oxygen Species - metabolism;Tobacco Smoke Pollution;Up-Regulation;Urinary Bladder Neoplasms
    日期: 2012-03-19
    上傳時間: 2026-04-23 11:12:16 (UTC+8)
    出版者: United States: American Chemical Society
    摘要: 摘要: Overexposure to biphenyl amine compounds, which are found in smoke and azo-dyes, is linked to the occurrence of bladder cancer. However, the molecular mechanisms of biphenyl amine compound-induced bladder cancer are still unclear. Many studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) in neoplastic lesions is associated with carcinogenesis. In this study, we have demonstrated that 2-aminobiphenyl (2-ABP) up-regulated the expression of COX-2 in a dose- and time-dependent manner in TSGH-8301 bladder cancer cells. This 2-ABP-induced COX-2 expression was attenuated by ROS scavenger NAC and NADPH oxidase inhibitors apocynin and DPI. The p22phox subunit of NADPH oxidase, but not p67, and Nox2 was up-regulated by 2-ABP. Knocking down p22phox by siRNA significantly reduced 2-ABP-induced COX-2 expression. Furthermore, 2-ABP also activated the ERK/JNK-AP1 pathways, and this effect was also abolished by NADPH oxidase inhibitors. Blocking the ERK/JNK-AP1 signaling pathways by pharmacological inhibitors attenuated 2-ABP-induced COX-2 expression. Overexpression of the upstream ERK activator MEK1 significantly and consistently increased 2-ABP-mediated COX-2 expression. Transfection of a dominant negative c-Jun mutant, TAM-67, blocked 2-ABP-mediated COX-2 expression, demonstrating that c-Jun was responsible for the transcriptional activation. Taken together, these results demonstrate that 2-ABP induces the carcinogenic factor COX-2 and that this induction is mediated through NADPH oxidase-derived ROS-dependent JNK/ERK-AP-1 pathways.
    其他題名: Chem. Res. Toxicol
    出版者: United States: American Chemical Society
    出版日期: 2012-03-19
    出處: Chemical Research in Toxicology, 2012-03, Vol.25 (3), p.695-705
    資源來源: American Chemical Society Journals
    版權: Copyright © 2012 American Chemical Society
    版權: 2012 American Chemical Society
    識別號: ISSN: 0893-228X
    識別號: ISSN: 1520-5010
    識別號: EISSN: 1520-5010
    識別號: DOI: 10.1021/tx2004689
    識別號: PMID: 22288910
    顯示於類別:[生命科學系] 期刊論文

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