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Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification
Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091760/ https://www.ncbi.nlm.nih.gov/pubmed/27806114 http://dx.doi.org/10.1371/journal.pone.0166090 |
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author | Su, Chia-Hsin Lin, I-Hsuan Tzeng, Tsai-Yu Hsieh, Wen-Ting Hsu, Ming-Ta |
author_facet | Su, Chia-Hsin Lin, I-Hsuan Tzeng, Tsai-Yu Hsieh, Wen-Ting Hsu, Ming-Ta |
author_sort | Su, Chia-Hsin |
collection | PubMed |
description | Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer. |
format | Online Article Text |
id | pubmed-5091760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50917602016-11-15 Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification Su, Chia-Hsin Lin, I-Hsuan Tzeng, Tsai-Yu Hsieh, Wen-Ting Hsu, Ming-Ta PLoS One Research Article Cytokines are low molecular weight regulatory proteins, or glycoproteins, with both tumor-promoting and inhibitory effects on breast cancer growth. Different cytokines play important roles in breast cancer initiation and progression. Here, we show that of the 39 interleukin (IL) genes, IL-20 is the only gene over-expressed in MCF-7 cells treated with estradiol (E2) and that induction of IL-20 expression by estrogen was epigenetically regulated. Methylation of histone H3K4 in the IL-20 promoter was shown to occur via the specific recruitment of KMT2B by estrogen receptor alpha (ERα), but not by other members of the mixed-lineage leukemia (MLL) family of histone methyltransferases. Depletion of KMT2B, or IL-20, disrupts estrogen signaling, attenuates cell proliferation, reduces colony formation, and results in cell cycle arrest. Furthermore, we demonstrated that KMT2B-mediated epigenetic modification also affected the expression of several ERα target genes. IL-20 and KMT2B expression were also associated with ERα-positive breast cancer tissues. We have revealed an important role for KMT2B in the epigenetic transcriptional regulation of cytokine IL-20, and other ERα-responsive genes, in breast cancer cells. Inhibition of IL-20 and KMT2B may have therapeutic benefits in ERα-positive breast cancer. Public Library of Science 2016-11-02 /pmc/articles/PMC5091760/ /pubmed/27806114 http://dx.doi.org/10.1371/journal.pone.0166090 Text en © 2016 Su et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Su, Chia-Hsin Lin, I-Hsuan Tzeng, Tsai-Yu Hsieh, Wen-Ting Hsu, Ming-Ta Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title | Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title_full | Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title_fullStr | Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title_full_unstemmed | Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title_short | Regulation of IL-20 Expression by Estradiol through KMT2B-Mediated Epigenetic Modification |
title_sort | regulation of il-20 expression by estradiol through kmt2b-mediated epigenetic modification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091760/ https://www.ncbi.nlm.nih.gov/pubmed/27806114 http://dx.doi.org/10.1371/journal.pone.0166090 |
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