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Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency
We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015082/ https://www.ncbi.nlm.nih.gov/pubmed/27604655 http://dx.doi.org/10.1038/srep33035 |
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author | Jung, Hae Hyun Lee, Soo-Hyeon Kim, Ji-Yeon Ahn, Jin Seok Park, Yeon Hee Im, Young-Hyuck |
author_facet | Jung, Hae Hyun Lee, Soo-Hyeon Kim, Ji-Yeon Ahn, Jin Seok Park, Yeon Hee Im, Young-Hyuck |
author_sort | Jung, Hae Hyun |
collection | PubMed |
description | We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. |
format | Online Article Text |
id | pubmed-5015082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50150822016-09-12 Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency Jung, Hae Hyun Lee, Soo-Hyeon Kim, Ji-Yeon Ahn, Jin Seok Park, Yeon Hee Im, Young-Hyuck Sci Rep Article We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4. We demonstrated that ETS1 mRNA and protein were overexpressed in TNBC cells compared with other BC cell lines (P = <0.001) and DUSP4 mRNA was downregulated (P = <0.001). MTT viability assay showed that simvastatin had significant antitumor activity (P = 0.002 in 0.1 μM). In addition, simvastatin could restore dusp4 deficiency and suppress ets-1 expression in TNBC. Lastly, we found that si-DUSP4 RNA transfection overcame the antitumor activity of statins. MAPK pathway inhibitor, U0126 and PI3KCA inhibitor LY294002 also decreased levels of ets-1, phosphor-ERK and phosphor-AKT on Western blot assay. Accordingly, our study indicates that simvastatin potentially affects the activity of transcriptional factors such as ets-1 and dusp4 through the MAPK pathway. In conclusion, statins might be potential candidates for TNBC therapy reducing ets-1 expression via overexpression of dusp4. Nature Publishing Group 2016-09-08 /pmc/articles/PMC5015082/ /pubmed/27604655 http://dx.doi.org/10.1038/srep33035 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Jung, Hae Hyun Lee, Soo-Hyeon Kim, Ji-Yeon Ahn, Jin Seok Park, Yeon Hee Im, Young-Hyuck Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title | Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title_full | Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title_fullStr | Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title_full_unstemmed | Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title_short | Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency |
title_sort | statins affect ets1-overexpressing triple-negative breast cancer cells by restoring dusp4 deficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015082/ https://www.ncbi.nlm.nih.gov/pubmed/27604655 http://dx.doi.org/10.1038/srep33035 |
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