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HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway

Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, anne...

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Autores principales: Park, Seung-Ho, Kim, Hyunhee, Kwak, Sungmin, Jeong, Ji-Hoon, Lee, Jangho, Hwang, Jin-Taek, Choi, Hyo-Kyoung, Choi, Kyung-Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290399/
https://www.ncbi.nlm.nih.gov/pubmed/32455774
http://dx.doi.org/10.3390/cells9051280
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author Park, Seung-Ho
Kim, Hyunhee
Kwak, Sungmin
Jeong, Ji-Hoon
Lee, Jangho
Hwang, Jin-Taek
Choi, Hyo-Kyoung
Choi, Kyung-Chul
author_facet Park, Seung-Ho
Kim, Hyunhee
Kwak, Sungmin
Jeong, Ji-Hoon
Lee, Jangho
Hwang, Jin-Taek
Choi, Hyo-Kyoung
Choi, Kyung-Chul
author_sort Park, Seung-Ho
collection PubMed
description Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3–ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3–ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3–ERα complex and substitution of the occupancy on the promoter by the p53–p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3–ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies.
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spelling pubmed-72903992020-06-15 HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway Park, Seung-Ho Kim, Hyunhee Kwak, Sungmin Jeong, Ji-Hoon Lee, Jangho Hwang, Jin-Taek Choi, Hyo-Kyoung Choi, Kyung-Chul Cells Article Tumor necrosis factor-α (TNF-α) plays a significant role in inflammation and cancer-related apoptosis. We identified a TNF-α-mediated epigenetic mechanism of apoptotic cell death regulation in estrogen receptor-α (ERα)-positive human breast cancer cells. To assess the apoptotic effect of TNF-α, annexin V/ propidium iodide (PI) double staining, cell viability assays, and Western blotting were performed. To elucidate this mechanism, histone deacetylase (HDAC) activity assay and immunoprecipitation (IP) were conducted; the mechanism was subsequently confirmed through chromatin IP (ChIP) assays. Finally, we assessed HDAC3–ERα-mediated apoptotic cell death after TNF-α treatment in ERα-positive human breast cancer (MCF-7) cells via the transcriptional activation of p53 target genes using luciferase assay and quantitative reverse transcription PCR. The TNF-α-induced selective apoptosis in MCF-7 cells was negatively regulated by the HDAC3–ERα complex in a caspase-7-dependent manner. HDAC3 possessed a p53-binding element, thus suppressing the transcriptional activity of its target genes. In contrast, MCF-7 cell treatment with TNF-α led to dissociation of the HDAC3–ERα complex and substitution of the occupancy on the promoter by the p53–p300 complex, thus accelerating p53 target gene expression. In this process, p53 stabilization was accompanied by its acetylation. This study showed that p53-mediated apoptosis in ERα-positive human breast cancer cells was negatively regulated by HDAC3–ERα in a caspase-7-dependent manner. Therefore, these proteins have potential application in therapeutic strategies. MDPI 2020-05-21 /pmc/articles/PMC7290399/ /pubmed/32455774 http://dx.doi.org/10.3390/cells9051280 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Park, Seung-Ho
Kim, Hyunhee
Kwak, Sungmin
Jeong, Ji-Hoon
Lee, Jangho
Hwang, Jin-Taek
Choi, Hyo-Kyoung
Choi, Kyung-Chul
HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title_full HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title_fullStr HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title_full_unstemmed HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title_short HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway
title_sort hdac3–erα selectively regulates tnf-α-induced apoptotic cell death in mcf-7 human breast cancer cells via the p53 signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290399/
https://www.ncbi.nlm.nih.gov/pubmed/32455774
http://dx.doi.org/10.3390/cells9051280
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