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IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575815/ https://www.ncbi.nlm.nih.gov/pubmed/33117284 http://dx.doi.org/10.3389/fendo.2020.568375 |
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author | Cervantes-Badillo, Mayte Guadalupe Paredes-Villa, Alejandro Gómez-Romero, Vania Cervantes-Roldán, Rafael Arias-Romero, Luis E. Villamar-Cruz, Olga González-Montiel, Miroslava Barrios-García, Tonatiuh Cabrera-Quintero, Alberto J. Rodríguez-Gómez, Gabriel Cancino-Villeda, Laura Zentella-Dehesa, Alejandro León-Del-Río, Alfonso |
author_facet | Cervantes-Badillo, Mayte Guadalupe Paredes-Villa, Alejandro Gómez-Romero, Vania Cervantes-Roldán, Rafael Arias-Romero, Luis E. Villamar-Cruz, Olga González-Montiel, Miroslava Barrios-García, Tonatiuh Cabrera-Quintero, Alberto J. Rodríguez-Gómez, Gabriel Cancino-Villeda, Laura Zentella-Dehesa, Alejandro León-Del-Río, Alfonso |
author_sort | Cervantes-Badillo, Mayte Guadalupe |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7575815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75758152020-10-27 IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells Cervantes-Badillo, Mayte Guadalupe Paredes-Villa, Alejandro Gómez-Romero, Vania Cervantes-Roldán, Rafael Arias-Romero, Luis E. Villamar-Cruz, Olga González-Montiel, Miroslava Barrios-García, Tonatiuh Cabrera-Quintero, Alberto J. Rodríguez-Gómez, Gabriel Cancino-Villeda, Laura Zentella-Dehesa, Alejandro León-Del-Río, Alfonso Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2020-10-07 /pmc/articles/PMC7575815/ /pubmed/33117284 http://dx.doi.org/10.3389/fendo.2020.568375 Text en Copyright © 2020 Cervantes-Badillo, Paredes-Villa, Gómez-Romero, Cervantes-Roldán, Arias-Romero, Villamar-Cruz, González-Montiel, Barrios-García, Cabrera-Quintero, Rodríguez-Gómez, Cancino-Villeda, Zentella-Dehesa and León-Del-Río http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Cervantes-Badillo, Mayte Guadalupe Paredes-Villa, Alejandro Gómez-Romero, Vania Cervantes-Roldán, Rafael Arias-Romero, Luis E. Villamar-Cruz, Olga González-Montiel, Miroslava Barrios-García, Tonatiuh Cabrera-Quintero, Alberto J. Rodríguez-Gómez, Gabriel Cancino-Villeda, Laura Zentella-Dehesa, Alejandro León-Del-Río, Alfonso IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title | IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title_full | IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title_fullStr | IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title_full_unstemmed | IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title_short | IFI27/ISG12 Downregulates Estrogen Receptor α Transactivation by Facilitating Its Interaction With CRM1/XPO1 in Breast Cancer Cells |
title_sort | ifi27/isg12 downregulates estrogen receptor α transactivation by facilitating its interaction with crm1/xpo1 in breast cancer cells |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575815/ https://www.ncbi.nlm.nih.gov/pubmed/33117284 http://dx.doi.org/10.3389/fendo.2020.568375 |
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