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Article

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

1
Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan
2
Faculty of Science, Mutah University, Karak 61710, Jordan
3
Hamdi Mango Center for Scientific Research, The University of Jordan, Amman 11942, Jordan
*
Author to whom correspondence should be addressed.
Academic Editors: Tiziana Angrisano and Michele Longo
Received: 26 March 2021 / Revised: 13 May 2021 / Accepted: 18 May 2021 / Published: 19 May 2021
(This article belongs to the Special Issue Deciphering Epigenetic Signature in Human Health and Disease)
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. View Full-Text
Keywords: LDHB hypomethylation; breast cancer; lactate; LDHA and LDHB gene expression; tamoxifen resistance LDHB hypomethylation; breast cancer; lactate; LDHA and LDHB gene expression; tamoxifen resistance
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MDPI and ACS Style

Hamadneh, L.; Al-Lakkis, L.; Alhusban, A.A.; Tarawneh, S.; Abu-Irmaileh, B.; Albustanji, S.; Al-Bawab, A.Q. Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line. Genes 2021, 12, 777. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12050777

AMA Style

Hamadneh L, Al-Lakkis L, Alhusban AA, Tarawneh S, Abu-Irmaileh B, Albustanji S, Al-Bawab AQ. Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line. Genes. 2021; 12(5):777. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12050777

Chicago/Turabian Style

Hamadneh, Lama, Lara Al-Lakkis, Ala A. Alhusban, Shahd Tarawneh, Bashaer Abu-Irmaileh, Sokiyna Albustanji, and Abdel Q. Al-Bawab 2021. "Changes in Lactate Production, Lactate Dehydrogenase Genes Expression and DNA Methylation in Response to Tamoxifen Resistance Development in MCF-7 Cell Line" Genes 12, no. 5: 777. https://0-doi-org.brum.beds.ac.uk/10.3390/genes12050777

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