ArticleMolecular cancer research : MCR2017
Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.
Article in Molecular cancer research : MCR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021Pooled it
- Effect of Bazedoxifene and Conjugated Estrogen (Duavee) on Breast Cancer Risk Biomarkers in High-Risk Women: A Pilot Study.Cancer prevention research (Philadelphia, Pa.) · 2019Trial
- Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer.Journal for immunotherapy of cancer · 2025Article
- Breaking Barriers in Breast Cancer: Multi-Targeted Therapeutic Insights.Mini reviews in medicinal chemistry · 2025Review
- Site-specific O-GlcNAcylation of progesterone receptor (PR) supports PR attenuation of interferon stimulated genes (ISGs) and tumor growth in breast cancer.The Journal of biological chemistry · 2024Article
- Article
- The duality of STAT2 mediated type I interferon signaling in the tumor microenvironment and chemoresistance.Cytokine · 2023Review
- Article
- The Divergent Effects of Ovarian Steroid Hormones in the MCF-7 Model for Luminal A Breast Cancer: Mechanistic Leads for Therapy.International journal of molecular sciences · 2022Review
- Progesterone promotes immunomodulation and tumor development in the murine mammary gland.Journal for immunotherapy of cancer · 2021Article
- UMP-CMP kinase 2 gene expression in macrophages is dependent on the IRF3-IFNAR signaling axis.PloS one · 2021Article
- The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway.Cellular & molecular immunology · 2020Article
- Type I interferons and related pathways in cell senescence.Aging cell · 2020Review
- Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.Molecular and cellular endocrinology · 2020Article
- 90 YEARS OF PROGESTERONE: Progesterone and progesterone receptors in breast cancer: past, present, future.Journal of molecular endocrinology · 2020Review
- KLF7 promotes pancreatic cancer growth and metastasis by up-regulating ISG expression and maintaining Golgi complex integrity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- MX 2 is a novel regulator of cell cycle in melanoma cells.Pigment cell & melanoma research · 2020Article
- Progesterone receptor promotes degradation of STAT2 to inhibit the interferon response in breast cancer.Oncoimmunology · 2020Article
- The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.Neuron · 2019Article
- Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy.Cancers · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to IFN treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR's ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. IFN activation is a critical early step in nascent tumor recognition and destruction through immunosurveillance. As the large majority of breast tumors are PR positive at the time of diagnosis, PR-dependent downregulation of IFN signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors.
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Registered trials
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