EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells

  • Authors:
    • Shouqiang Cao
    • Yubo Yan
    • Xiangyu Zhang
    • Kai Zhang
    • Cheng Liu
    • Guibin  Zhao
    • Jingquan Han
    • Qing Dong
    • Baozhong Shen
    • Anhua Wu
    • Jian Cui
  • View Affiliations

  • Published online on: May 23, 2011     https://doi.org/10.3892/ijo.2011.1053
  • Pages: 383-391
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Abstract

The epidermal growth factor receptor (EGFR) can be activated by several growth factors within the tumor microenvironment, and it can activate several signaling pathways. For tumor development, these EGFR-related signaling pathways may converge on several common nuclear transcription factors, one such transcription factor being STAT5. STAT5 plays an important role in the oncogenic signal transduction pathway in non-small cell lung cancer. In this study, we examined whether the epidermal growth factor (EGF) can stimulate cyclooxygenase-2 (COX-2) expression in human lung adeno­carcinoma A549 cells transfected with or without STAT5 siRNA or dominant-negative (DN)-STAT5, and identified the pathways involved in this response. We found that STAT5 siRNA significantly reduced EGF-induced COX-2 expression, and STAT5 phosphorylation. STAT5 phosphorylation predominantly mediates EGF-induced COX-2 promoter activity. STAT5 siRNA was found to inhibit COX-2 expression in resting A549 cells despite the absence of detectable activated phosphorylated STAT5. Using an adenoviral system, we expressed DN-STAT5 in human lung adenocarcinoma A549 cells in order to broaden the investigation and to determine the role of STAT5 in EGF-mediated COX-2 gene expression. The overexpression of DN-STAT5 significantly inhibited EGF-induced COX-2 expression, and we found that EGF induced the tyrosine phosphorylation of STAT5 and up- regulated COX-2 expression. DN-STAT5 also blocked COX-2 promoter activity. Our results demonstrate that EGF stimulates COX-2 expression in human lung adenocarcinoma A549 cells via the activation of the STAT5 pathway and that COX-2 expression may be independent of phosphorylated STAT5 in A549 cells in vitro.

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August 2011
Volume 39 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Cao S, Yan Y, Zhang X, Zhang K, Liu C, Zhao G, Han J, Dong Q, Shen B, Wu A, Wu A, et al: EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells. Int J Oncol 39: 383-391, 2011
APA
Cao, S., Yan, Y., Zhang, X., Zhang, K., Liu, C., Zhao, G. ... Cui, J. (2011). EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells. International Journal of Oncology, 39, 383-391. https://doi.org/10.3892/ijo.2011.1053
MLA
Cao, S., Yan, Y., Zhang, X., Zhang, K., Liu, C., Zhao, G., Han, J., Dong, Q., Shen, B., Wu, A., Cui, J."EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells". International Journal of Oncology 39.2 (2011): 383-391.
Chicago
Cao, S., Yan, Y., Zhang, X., Zhang, K., Liu, C., Zhao, G., Han, J., Dong, Q., Shen, B., Wu, A., Cui, J."EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells". International Journal of Oncology 39, no. 2 (2011): 383-391. https://doi.org/10.3892/ijo.2011.1053