ArticleMolecular cancer therapeutics2010
IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosis.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- Genes Associated with the Immune System Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model.Biology · 2024Article
- Article
- AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.Cancers · 2023Article
- The diverse repertoire of ISG15: more intricate than initially thought.Experimental & molecular medicine · 2022Review
- An Improved Model of Moderate Sleep Apnoea for Investigating Its Effect as a Comorbidity on Neurodegenerative Disease.Frontiers in aging neuroscience · 2022Article
- A Mathematical Model of Breast Tumor Progression Based on Immune Infiltration.Journal of personalized medicine · 2021Article
- Identification of genes modulated by interferon gamma in breast cancer cells.Biochemistry and biophysics reports · 2021Article
- Nuclear Mechanisms Involved in Endocrine Resistance.Frontiers in oncology · 2021Review
- Review
- Enhanced mitochondrial pyruvate transport elicits a robust ROS production to sensitize the antitumor efficacy of interferon-γ in colon cancer.Redox biology · 2019Article
- Weighted Fused Pathway Graphical Lasso for Joint Estimation of Multiple Gene Networks.Frontiers in genetics · 2019Article
- Interferon γ suppresses dentin sialophosphoprotein in oral squamous cell carcinoma cells resulting in antitumor effects, via modulation of the endoplasmic reticulum response.International journal of oncology · 2018Article
- Interferon regulatory factor 1 inactivation in human cancer.Bioscience reports · 2018Review
- Molecular mechanism of activated T cells in breast cancer.OncoTargets and therapy · 2018Article
- BRCA1-mimetic compound NSC35446.HCl inhibits IKKB expression by reducing estrogen receptor-α occupancy in the IKKB promoter and inhibits NF-κB activity in antiestrogen-resistant human breast cancer cells.Breast cancer research and treatment · 2017Article
- Transcriptional profile of breast muscle in heat stressed layers is similar to that of broiler chickens at control temperature.Genetics, selection, evolution : GSE · 2017Article
- Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway.Oncotarget · 2017Article
- Blockade of IDO-kynurenine-AhR metabolic circuitry abrogates IFN-γ-induced immunologic dormancy of tumor-repopulating cells.Nature communications · 2017Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Antiestrogens are effective therapies for the management of many estrogen receptor-alpha (ER)-positive breast cancers. Nonetheless, both de novo and acquired resistance occur and remain major problems in the clinical setting. IFNgamma is an inflammatory cytokine that induces the expression and function of IFN regulatory factor 1 (IRF1), a tumor suppressor gene that can increase antiestrogen responsiveness. We show that IFNgamma, but not IFNalpha, IFNbeta, or fulvestrant (ICI; ICI 182,780; Faslodex), induces IRF1 expression in antiestrogen-resistant MCF7/LCC9 and LY2 cells. Moreover, IFNgamma restores the responsiveness of these cells to fulvestrant. Increased IRF1 activation suppresses NF-kappaB p65 (RELA) activity, inhibits the expression of prosurvival (BCL2, BCL-W), and induces the expression of proapoptotic members (BAK, mitochondrial BAX) of the BCL2 family. This molecular signaling is associated with the activation of signal transducer and activator of transcription 1 and leads to increased mitochondrial membrane permeability; activation of caspase-7 (CASP7), CASP8, and CASP9; and induction of apoptosis but not autophagy. Whereas antiestrogen-resistant cells are capable of inducing autophagy through IFN-mediated signaling, their ability to do so through antiestrogen-regulated signaling is lost. The abilities of IFNgamma to activate CASP8, induce apoptosis, and restore antiestrogen sensitivity are prevented by siRNA targeting IRF1, whereas transient overexpression of IRF1 mimics the effects of IFNgamma treatment. These observations support the exploration of clinical trials combining antiestrogens and compounds that can induce IRF1, such as IFNgamma, for the treatment of some ER-positive breast cancers.
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