Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells
- PMID: 17452973
- DOI: 10.1038/sj.onc.1210470
Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells
Abstract
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.
Similar articles
-
The interferon-induced protein kinase (PKR), triggers apoptosis through FADD-mediated activation of caspase 8 in a manner independent of Fas and TNF-alpha receptors.Oncogene. 2000 Jul 27;19(32):3665-74. doi: 10.1038/sj.onc.1203710. Oncogene. 2000. PMID: 10951573
-
Theaflavins target Fas/caspase-8 and Akt/pBad pathways to induce apoptosis in p53-mutated human breast cancer cells.Carcinogenesis. 2010 Feb;31(2):259-68. doi: 10.1093/carcin/bgp240. Epub 2009 Dec 7. Carcinogenesis. 2010. PMID: 19969555
-
Intracellular mechanisms mediating tocotrienol-induced apoptosis in neoplastic mammary epithelial cells.Asia Pac J Clin Nutr. 2005;14(4):366-73. Asia Pac J Clin Nutr. 2005. PMID: 16326643
-
Interferon-gamma and TRAIL in human breast tumor cells.Vitam Horm. 2004;67:291-318. doi: 10.1016/S0083-6729(04)67016-6. Vitam Horm. 2004. PMID: 15110183 Review.
-
Caspase-8 in apoptosis: the beginning of "the end"?IUBMB Life. 2000 Aug;50(2):85-90. doi: 10.1080/713803693. IUBMB Life. 2000. PMID: 11185963 Review.
Cited by
-
MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells.Oncol Rep. 2016 Aug;36(2):633-40. doi: 10.3892/or.2016.4864. Epub 2016 Jun 9. Oncol Rep. 2016. PMID: 27279136 Free PMC article.
-
Effects of IFN-γ on the proliferation of 32D cells expressing Akt after IRF-1 gene silencing.Transl Cancer Res. 2021 Jan;10(1):327-336. doi: 10.21037/tcr-20-1866. Transl Cancer Res. 2021. PMID: 35116263 Free PMC article.
-
MicroRNA-301a (miR-301a) is induced in hepatocellular carcinoma (HCC) and down- regulates the expression of interferon regulatory factor-1.Biochem Biophys Res Commun. 2020 Apr 2;524(2):273-279. doi: 10.1016/j.bbrc.2020.01.034. Epub 2020 Jan 25. Biochem Biophys Res Commun. 2020. PMID: 31987500 Free PMC article.
-
Identification of a natural compound by cell-based screening that enhances interferon regulatory factor-1 activity and causes tumor suppression.Mol Cancer Ther. 2011 Oct;10(10):1774-83. doi: 10.1158/1535-7163.MCT-11-0304. Epub 2011 Aug 4. Mol Cancer Ther. 2011. PMID: 21817116 Free PMC article.
-
Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response.Br J Cancer. 2018 Jan;118(1):62-71. doi: 10.1038/bjc.2017.389. Epub 2017 Nov 7. Br J Cancer. 2018. PMID: 29112686 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous