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Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells.

Publication ,  Journal Article
Stang, MT; Armstrong, MJ; Watson, GA; Sung, KY; Liu, Y; Ren, B; Yim, JH
Published in: Oncogene
September 27, 2007

Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has apoptotic anti-tumor activity. In breast cancer cell types, IRF-1 is implicated in mediating apoptosis by both novel and established anti-tumor agents, including the anti-estrogens tamoxifen and faslodex. Here we demonstrate that in MDA468 breast cancer cells, apoptosis by IFN-gamma is mediated by IRF-1 and IFN-gamma, and IRF-1-induced apoptosis is caspase-mediated. IRF-1 induction results in cleavage of caspase-8, -3 and -7, and application of caspase inhibitors attenuate activated cleavage products. IRF-1-induced apoptosis involves caspase-8 since apoptosis is significantly decreased by the caspase-8-specific inhibitor IETD, c-FLIP expression and in caspase-8-deficient cancer cells. Furthermore, we demonstrate that IRF-1-induced apoptosis requires fas-associated death domain (FADD) since dominant-negative FADD expressing cells resist IRF-1-induced apoptosis and activated downstream products. Immunofluorescent studies demonstrate perinuclear colocalization of FADD and caspase-8. Despite the known role of FADD in mediating death-ligand induced apoptosis, neutralizing antibodies against classical death receptors do not inhibit IRF-1 induced apoptosis, and no secreted ligand appears to be involved since MDA468 coincubated with IRF-1 transfected cells do not apoptose. Therefore, we demonstrate that IRF-1 induces a ligand-independent FADD/caspase-8-mediated apoptosis in breast cancer cells.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

September 27, 2007

Volume

26

Issue

44

Start / End Page

6420 / 6430

Location

England

Related Subject Headings

  • fas Receptor
  • Tumor Cells, Cultured
  • TNF-Related Apoptosis-Inducing Ligand
  • Subcellular Fractions
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Oncology & Carcinogenesis
  • Ligands
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Stang, M. T., Armstrong, M. J., Watson, G. A., Sung, K. Y., Liu, Y., Ren, B., & Yim, J. H. (2007). Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells. Oncogene, 26(44), 6420–6430. https://doi.org/10.1038/sj.onc.1210470
Stang, M. T., M. J. Armstrong, G. A. Watson, K. Y. Sung, Y. Liu, B. Ren, and J. H. Yim. “Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells.Oncogene 26, no. 44 (September 27, 2007): 6420–30. https://doi.org/10.1038/sj.onc.1210470.
Stang MT, Armstrong MJ, Watson GA, Sung KY, Liu Y, Ren B, et al. Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells. Oncogene. 2007 Sep 27;26(44):6420–30.
Stang, M. T., et al. “Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells.Oncogene, vol. 26, no. 44, Sept. 2007, pp. 6420–30. Pubmed, doi:10.1038/sj.onc.1210470.
Stang MT, Armstrong MJ, Watson GA, Sung KY, Liu Y, Ren B, Yim JH. Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells. Oncogene. 2007 Sep 27;26(44):6420–6430.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

September 27, 2007

Volume

26

Issue

44

Start / End Page

6420 / 6430

Location

England

Related Subject Headings

  • fas Receptor
  • Tumor Cells, Cultured
  • TNF-Related Apoptosis-Inducing Ligand
  • Subcellular Fractions
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Oncology & Carcinogenesis
  • Ligands