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IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition.

Publication ,  Journal Article
Armstrong, MJ; Stang, MT; Liu, Y; Yan, J; Pizzoferrato, E; Yim, JH
Published in: Cancer Biol Ther
2015

Interferon Regulatory Factor (IRF)-1, originally identified as a transcription factor of the human interferon (IFN)-β gene, mediates tumor suppression and may inhibit oncogenesis. We have shown that IRF-1 in human breast cancer cells results in the down-regulation of survivin, tumor cell death, and the inhibition of tumor growth in vivo in xenogeneic mouse models. In this current report, we initiate studies comparing the effect of IRF-1 in human nonmalignant breast cell and breast cancer cell lines. While IRF-1 in breast cancer cells results in growth inhibition and cell death, profound growth inhibition and cell death are not observed in nonmalignant human breast cells. We show that TNF-α or IFN-γ induces IRF-1 in breast cancer cells and results in enhanced cell death. Abrogation of IRF-1 diminishes TNF-α and IFN-γ-induced apoptosis. We test the hypothesis that IRF-1 augments TNF-α-induced apoptosis in breast cancer cells. Potential signaling networks elicited by IRF-1 are investigated by evaluating the NF-κB pathway. TNF-α and/or IFN-γ results in decreased presence of NF-κB p65 in the nucleus of breast cancer cells. While TNF-α and/or IFN-γ can induce IRF-1 in nonmalignant breast cells, a marked change in NF-κB p65 is not observed. Moreover, the ectopic expression of IRF-1 in breast cancer cells results in caspase-3, -7, -8 cleavage, inhibits NF-κB activity, and suppresses the expression of molecules involved in the NF-κB pathway. These data show that IRF-1 in human breast cancer cells elicits multiple signaling networks including intrinsic and extrinsic cell death and down-regulates molecules involved in the NF-κB pathway.

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Published In

Cancer Biol Ther

DOI

EISSN

1555-8576

Publication Date

2015

Volume

16

Issue

7

Start / End Page

1029 / 1041

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription Factor RelA
  • TNF Receptor-Associated Factor 2
  • Signal Transduction
  • RNA Interference
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interferon-gamma
  • Interferon Regulatory Factor-1
  • Inhibitor of Apoptosis Proteins
 

Citation

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ICMJE
MLA
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Armstrong, M. J., Stang, M. T., Liu, Y., Yan, J., Pizzoferrato, E., & Yim, J. H. (2015). IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition. Cancer Biol Ther, 16(7), 1029–1041. https://doi.org/10.1080/15384047.2015.1046646
Armstrong, Michaele J., Michael T. Stang, Ye Liu, Jin Yan, Eva Pizzoferrato, and John H. Yim. “IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition.Cancer Biol Ther 16, no. 7 (2015): 1029–41. https://doi.org/10.1080/15384047.2015.1046646.
Armstrong MJ, Stang MT, Liu Y, Yan J, Pizzoferrato E, Yim JH. IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition. Cancer Biol Ther. 2015;16(7):1029–41.
Armstrong, Michaele J., et al. “IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition.Cancer Biol Ther, vol. 16, no. 7, 2015, pp. 1029–41. Pubmed, doi:10.1080/15384047.2015.1046646.
Armstrong MJ, Stang MT, Liu Y, Yan J, Pizzoferrato E, Yim JH. IRF-1 inhibits NF-κB activity, suppresses TRAF2 and cIAP1 and induces breast cancer cell specific growth inhibition. Cancer Biol Ther. 2015;16(7):1029–1041.

Published In

Cancer Biol Ther

DOI

EISSN

1555-8576

Publication Date

2015

Volume

16

Issue

7

Start / End Page

1029 / 1041

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Transcription Factor RelA
  • TNF Receptor-Associated Factor 2
  • Signal Transduction
  • RNA Interference
  • Oncology & Carcinogenesis
  • NF-kappa B
  • Interferon-gamma
  • Interferon Regulatory Factor-1
  • Inhibitor of Apoptosis Proteins