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Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma

  • Genotoxicity and Carcinogenicity
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Abstract

Fibroblast growth factor (FGF)-9 belongs to the FGF family which modulate cell proliferation, differentiation, and motility. Benzo(a)pyrene is a polycyclic aromatic hydrocarbon (PAH) and ubiquitous environmental carcinogen present in automobile exhaust, cigarette smoke, and foods. The major purposes of this study were to explore the roles of FGF-9 in the benzo(a)pyrene-induced lung cancer invasion in vitro and the metastatic development of lung adenocarcinoma in human. The data of RT-PCR analysis indicated that treatments of human lung adenocarcinoma CL5 cells with benzo(a)pyrene and a PAH mixture motorcycle exhaust particulate (MEP) extracts increased FGF-9 mRNA expression. The increased expression was blocked by cotreatments with a p38 mitogen-activated protein kinase inhibitor SB202190 and an extracellular signal-regulated kinase inhibitor PD98059. The results of immunoblot analysis and Matrigel assay showed that benzo(a)pyrene and MEP extracts produced a concomitant induction of FGF-9 protein and invasive ability of CL5 cells. The benzo(a)pyrene- and MEP-induced invasion was suppressed by FGF-9 neutralizing antibodies. The results of immunohistochemistry analysis of human lung adenocarcinoma specimens showed that FGF-9 protein was detected in the adenocarcinoma cells but not in normal epithelium. FGF-9 staining intensity was positively correlated with status of disease and degree of lymph node metastasis in these lung adenocarcinomas. These present findings suggest that FGF-9 has potential roles in benzo(a)pyrene-induced CL5 cell invasion and human lung adenocarcinoma metastasis.

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Acknowledgments

This work was supported by grants NSC95-2314-B002-256-MY3 from the National Science Council and DOH94-TD-G-111-031 from the Department of Health, R.O.C.

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There were no conflicts of interest in this work.

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Authors and Affiliations

  1. Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei, Taiwan, ROC

    Tzuu-Huei Ueng, Yi-Ya Tsai, Jen-Liang Su, Ping-Kun Chan & Min-Liang Kuo

  2. Department of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

    Yih-Leong Chang

  3. Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

    Jin-Yuan Shih

  4. Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

    Yung-Chie Lee

  5. Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan, ROC

    Yee-Chung Ma

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  1. Tzuu-Huei Ueng
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Correspondence to Tzuu-Huei Ueng.

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Ueng, TH., Chang, YL., Tsai, YY. et al. Potential roles of fibroblast growth factor-9 in the benzo(a)pyrene-induced invasion in vitro and the metastasis of human lung adenocarcinoma. Arch Toxicol 84, 651–660 (2010). https://doi.org/10.1007/s00204-010-0547-3

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  • DOI: https://doi.org/10.1007/s00204-010-0547-3

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