Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB

  • Authors:
    • Eduardo Parra
    • Jorge Ferreira
    • Leonardo Saenz
  • View Affiliations

  • Published online on: July 8, 2011     https://doi.org/10.3892/ijmm.2011.745
  • Pages: 847-853
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Abstract

Previous studies suggest that the effects of Egr-1 on tumorigenesis are critically dependent on the levels of Egr-1 and the cellular context. For this reason, we examined the effects of blocking the Egr-1 activity by a short interfering RNA (siRNA) against Egr-1 on the expression of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) signaling in the PC-3 and LNCaP prostate carcinoma cell lines. We observed that the reduction in expression of Egr-1 in PC-3 and LNCaP cells by effects of the siRNA vector resulted in lower cell viability and increased apoptosis at 24 and 120 h after transfection. This reduced cell viability correlated well with a reduced activity of the NF-κB and AP-1 factors. We analyzed the expression and activity of these factors and found that p65 and IκB but not p50 were reduced in the siRNA-treated cells. Similarly, we found that c-Fos but not c-Jun was reduced in the siRNA treated cells. These effects were translated to reduced transcriptional activity of NF-κB over cellular inhibitor of apoptosis (cIAP) and p21 genes, as assayed by RT-PCR and of AP-1 over a luciferase reporter activated by AP-1 response elements. Egr-1 was also found to interact directly with p65 and IκB members of the NF-κB family, thereby was able to regulate directly their activity by post-transcriptional effects. These results suggest that Egr-1 may promote prostate cancer development by modulating the activity of factors NF-κB and AP-1, which are involved in cell proliferation and apoptosis.

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November 2011
Volume 28 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Parra E, Ferreira J and Saenz L: Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB. Int J Mol Med 28: 847-853, 2011.
APA
Parra, E., Ferreira, J., & Saenz, L. (2011). Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB. International Journal of Molecular Medicine, 28, 847-853. https://doi.org/10.3892/ijmm.2011.745
MLA
Parra, E., Ferreira, J., Saenz, L."Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB". International Journal of Molecular Medicine 28.5 (2011): 847-853.
Chicago
Parra, E., Ferreira, J., Saenz, L."Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB". International Journal of Molecular Medicine 28, no. 5 (2011): 847-853. https://doi.org/10.3892/ijmm.2011.745