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Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development

Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to known human carcinogens including dioxins can lead to the promotion of breast cancer. While the repressor protein of the AhR (AhRR) blocks the canonical AhR pathway, the function of AhRR in the development of breast...

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Autores principales: Vogel, Christoph F. A., Lazennec, Gwendal, Kado, Sarah Y., Dahlem, Carla, He, Yi, Castaneda, Alejandro, Ishihara, Yasuhiro, Vogeley, Christian, Rossi, Andrea, Haarmann-Stemmann, Thomas, Jugan, Juliann, Mori, Hidetoshi, Borowsky, Alexander D., La Merrill, Michele A., Sweeney, Colleen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982668/
https://www.ncbi.nlm.nih.gov/pubmed/33763068
http://dx.doi.org/10.3389/fimmu.2021.625346
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author Vogel, Christoph F. A.
Lazennec, Gwendal
Kado, Sarah Y.
Dahlem, Carla
He, Yi
Castaneda, Alejandro
Ishihara, Yasuhiro
Vogeley, Christian
Rossi, Andrea
Haarmann-Stemmann, Thomas
Jugan, Juliann
Mori, Hidetoshi
Borowsky, Alexander D.
La Merrill, Michele A.
Sweeney, Colleen
author_facet Vogel, Christoph F. A.
Lazennec, Gwendal
Kado, Sarah Y.
Dahlem, Carla
He, Yi
Castaneda, Alejandro
Ishihara, Yasuhiro
Vogeley, Christian
Rossi, Andrea
Haarmann-Stemmann, Thomas
Jugan, Juliann
Mori, Hidetoshi
Borowsky, Alexander D.
La Merrill, Michele A.
Sweeney, Colleen
author_sort Vogel, Christoph F. A.
collection PubMed
description Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to known human carcinogens including dioxins can lead to the promotion of breast cancer. While the repressor protein of the AhR (AhRR) blocks the canonical AhR pathway, the function of AhRR in the development of breast cancer is not well-known. In the current study we examined the impact of suppressing AhR activity using its dedicated repressor protein AhRR. AhRR is a putative tumor suppressor and is silenced in several cancer types, including breast, where its loss correlates with shorter patient survival. Using the AhRR transgenic mouse, we demonstrate that AhRR overexpression opposes AhR-driven and inflammation-induced growth of mammary tumors in two different murine models of breast cancer. These include a syngeneic model using E0771 mammary tumor cells as well as the Polyoma Middle T antigen (PyMT) transgenic model. Further AhRR overexpression or knockout of AhR in human breast cancer cells enhanced apoptosis induced by chemotherapeutics and inhibited the growth of mouse mammary tumor cells. This study provides the first in vivo evidence that AhRR suppresses mammary tumor development and suggests that strategies which lead to its functional restoration and expression may have therapeutic benefit.
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spelling pubmed-79826682021-03-23 Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development Vogel, Christoph F. A. Lazennec, Gwendal Kado, Sarah Y. Dahlem, Carla He, Yi Castaneda, Alejandro Ishihara, Yasuhiro Vogeley, Christian Rossi, Andrea Haarmann-Stemmann, Thomas Jugan, Juliann Mori, Hidetoshi Borowsky, Alexander D. La Merrill, Michele A. Sweeney, Colleen Front Immunol Immunology Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to known human carcinogens including dioxins can lead to the promotion of breast cancer. While the repressor protein of the AhR (AhRR) blocks the canonical AhR pathway, the function of AhRR in the development of breast cancer is not well-known. In the current study we examined the impact of suppressing AhR activity using its dedicated repressor protein AhRR. AhRR is a putative tumor suppressor and is silenced in several cancer types, including breast, where its loss correlates with shorter patient survival. Using the AhRR transgenic mouse, we demonstrate that AhRR overexpression opposes AhR-driven and inflammation-induced growth of mammary tumors in two different murine models of breast cancer. These include a syngeneic model using E0771 mammary tumor cells as well as the Polyoma Middle T antigen (PyMT) transgenic model. Further AhRR overexpression or knockout of AhR in human breast cancer cells enhanced apoptosis induced by chemotherapeutics and inhibited the growth of mouse mammary tumor cells. This study provides the first in vivo evidence that AhRR suppresses mammary tumor development and suggests that strategies which lead to its functional restoration and expression may have therapeutic benefit. Frontiers Media S.A. 2021-03-08 /pmc/articles/PMC7982668/ /pubmed/33763068 http://dx.doi.org/10.3389/fimmu.2021.625346 Text en Copyright © 2021 Vogel, Lazennec, Kado, Dahlem, He, Castaneda, Ishihara, Vogeley, Rossi, Haarmann-Stemmann, Jugan, Mori, Borowsky, La Merrill and Sweeney. 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 Immunology
Vogel, Christoph F. A.
Lazennec, Gwendal
Kado, Sarah Y.
Dahlem, Carla
He, Yi
Castaneda, Alejandro
Ishihara, Yasuhiro
Vogeley, Christian
Rossi, Andrea
Haarmann-Stemmann, Thomas
Jugan, Juliann
Mori, Hidetoshi
Borowsky, Alexander D.
La Merrill, Michele A.
Sweeney, Colleen
Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title_full Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title_fullStr Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title_full_unstemmed Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title_short Targeting the Aryl Hydrocarbon Receptor Signaling Pathway in Breast Cancer Development
title_sort targeting the aryl hydrocarbon receptor signaling pathway in breast cancer development
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982668/
https://www.ncbi.nlm.nih.gov/pubmed/33763068
http://dx.doi.org/10.3389/fimmu.2021.625346
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