4.7 Article

Aryl hydrocarbon receptor activation and overexpression upregulated fibroblast growth factor-9 in human lung adenocarcinomas

期刊

INTERNATIONAL JOURNAL OF CANCER
卷 125, 期 4, 页码 807-815

出版社

WILEY
DOI: 10.1002/ijc.24348

关键词

aryl hydrocarbon receptor; fibroblast growth factor-9; lung adenocarcinoma

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资金

  1. National Science Council, Taiwan, Republic of China [NSC95-2314-B-400-010-MY3]
  2. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Taiwan, Republic of China [EO-097PP-02]

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We had previously reported that aryl hydrocarbon receptors (AhRs) are overexpressed in lung adenocarcinomas. Benzo[a]pyrene (BaP), an AhR agonist, increased FGF-9 expression in human lung adenocarcinoma cells. Similarly, several AhR agonists increased FGF-9 mRNA levels, and BaP-induced FGF-9 expression was prevented by cotreatment with AhR antagonist in human lung adenocarcinomna cells. Furthermore, AhR agonists increased transcriptional activity of FGF-9 promoter. Modulation of AhR expression via RNA interference or transient overexpression respectively reduced or increased both constitutive and BaP-induced FGF-9 expression in human lung cells. These results suggested that AhR activation and overexpression increased FGF-9 expression in lung cells. FGF-9 increased growth of lung fibroblasts but not that of lung adenocarcinoma cells. However, conditioned media collected from FGF-9-treated fibroblasts increased cell growth of lung adenocarcinoma cells. Furthermore, lung adenocarcinoma cells expressed FGF receptor 2 and cotreatment with anti-FGF receptor 2 prevented the interaction between fibroblasts and tumor cells. It is likely that FGF-9-stimulated fibroblasts secreted unknown factors, which activated FGF receptor 2 and subsequently promoted growth of lung adenocarcinoma cells. We further compared AhR and FGF-9 expression in 146 non-small cell lung cancer (NSCLC) cases by immunohistochemistry. FGF-9 expression was more common in adenocarcinomas than in squamous cell carcinomas. Furthermore, FGF-9 and AhR expression were well correlated in lung adenocarcinomas. These results suggest that AhR expression correlated positively with FGF-9 expression in lung adenocarcinomas, which might promote tumor growth by modulating communication between tumor cells and fibroblasts. Preventing AhR overexpression or disturbing FGF-9 function may reduce the development of lung adenocarcinomas. (C) 2009 UICC

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