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Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line

Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate c...

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Autores principales: Hamadneh, Lama, Al-Lakkis, Lara, Alhusban, Ala A., Tarawneh, Shahd, Abu-Irmaileh, Bashaer, Albustanji, Sokiyna, Al-Bawab, Abdel Qader
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160872/
https://www.ncbi.nlm.nih.gov/pubmed/34069745
http://dx.doi.org/10.3390/genes12050777
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author Hamadneh, Lama
Al-Lakkis, Lara
Alhusban, Ala A.
Tarawneh, Shahd
Abu-Irmaileh, Bashaer
Albustanji, Sokiyna
Al-Bawab, Abdel Qader
author_facet Hamadneh, Lama
Al-Lakkis, Lara
Alhusban, Ala A.
Tarawneh, Shahd
Abu-Irmaileh, Bashaer
Albustanji, Sokiyna
Al-Bawab, Abdel Qader
author_sort Hamadneh, Lama
collection PubMed
description Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined LDHB promoter methylation levels. An upregulation of 2.9 times of LDHB gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in LDHA gene expression levels was found. Furthermore, morphological changes in the cell shape accompanied the changes in gene expression. Bisulfate treatment followed by sequencing of the LDHB promoter was performed to track any change in methylation levels; hypomethylation of CpG areas was found, suggesting that gene expression upregulation could be due to methylation level changes. Changes in LDHA and LDHB gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells.
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spelling pubmed-81608722021-05-29 Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line Hamadneh, Lama Al-Lakkis, Lara Alhusban, Ala A. Tarawneh, Shahd Abu-Irmaileh, Bashaer Albustanji, Sokiyna Al-Bawab, Abdel Qader Genes (Basel) Article Lactate dehydrogenase (LDH) is a key enzyme in the last step of glycolysis, playing a role in the pyruvate-to-lactate reaction. It is associated with the prognosis and metastasis of many cancers, including breast cancer. In this study, we investigated the changes in LDH gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined LDHB promoter methylation levels. An upregulation of 2.9 times of LDHB gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in LDHA gene expression levels was found. Furthermore, morphological changes in the cell shape accompanied the changes in gene expression. Bisulfate treatment followed by sequencing of the LDHB promoter was performed to track any change in methylation levels; hypomethylation of CpG areas was found, suggesting that gene expression upregulation could be due to methylation level changes. Changes in LDHA and LDHB gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells. MDPI 2021-05-19 /pmc/articles/PMC8160872/ /pubmed/34069745 http://dx.doi.org/10.3390/genes12050777 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hamadneh, Lama
Al-Lakkis, Lara
Alhusban, Ala A.
Tarawneh, Shahd
Abu-Irmaileh, Bashaer
Albustanji, Sokiyna
Al-Bawab, Abdel Qader
Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title_full Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title_fullStr Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title_full_unstemmed Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title_short Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line
title_sort changes in lactate production, lactate dehydrogenase genes expression and dna methylation in response to tamoxifen resistance development in mcf-7 cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160872/
https://www.ncbi.nlm.nih.gov/pubmed/34069745
http://dx.doi.org/10.3390/genes12050777
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