ArticleFrontiers in endocrinology2020
IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells.
Article in Frontiers in endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 32 citations in OpenAlex.
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- The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol.Oncology letters · 2024Article
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- Microarray data reveal potential genes that regulate triple-negative breast cancer.The Journal of international medical research · 2022Article
- The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.International journal of molecular sciences · 2022Article
- Anti-Tumoral Effect of Chemerin on Ovarian Cancer Cell Lines Mediated by Activation of Interferon Alpha Response.Cancers · 2022Article
- A Regulatory Axis between Epithelial Splicing Regulatory Proteins and Estrogen Receptor α Modulates the Alternative Transcriptome of Luminal Breast Cancer.International journal of molecular sciences · 2022Article
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- Visualization of the protein-protein interactions of hormone receptors in hormone-dependent cancer research.Endocrine oncology (Bristol, England) · 2022Review
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- RhoC Modulates Cell Junctions and Type I Interferon Response in Aggressive Breast Cancers.Frontiers in oncology · 2021Article
- Prediction of Key Candidate Genes for Platinum Resistance in Ovarian Cancer.International journal of general medicine · 2021Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
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Abstract
The estrogen receptor alpha (ERα) is a ligand-activated transcription factor whose activity is modulated by its interaction with multiple protein complexes. In this work, we have identified the protein interferon alpha inducible protein 27 (IFI27/ISG12) as a novel ERα-associated protein. IFI27/ISG12 transcription is regulated by interferon and estradiol and its overexpression is associated to reduced overall survival in ER+ breast cancer patients but its function in mammary gland tissue remains elusive. In this study we showed that overexpression of IFI27/ISG12 in breast cancer cells attenuates ERα transactivation activity and the expression of ERα-dependent genes. Our results demonstrated that IFI27/ISG12 overexpression in MCF-7 cells reduced their proliferation rate in 2-D and 3-D cell culture assays and impaired their ability to migrate in a wound-healing assay. We show that IFI27/ISG12 downregulation of ERα transactivation activity is mediated by its ability to facilitate the interaction between ERα and CRM1/XPO1 that mediates the nuclear export of large macromolecules to the cytoplasm. IFI27/ISG12 overexpression was shown to impair the estradiol-dependent proliferation and tamoxifen-induced apoptosis in breast cancer cells. Our results suggest that IFI27/ISG12 may be an important factor in regulating ERα activity in breast cancer cells by modifying its nuclear versus cytoplasmic protein levels. We propose that IFI27/ISG12 may be a potential target of future strategies to control the growth and proliferation of ERα-positive breast cancer tumors.
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