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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.

Authors
  • Hamadneh, Lama1
  • Al-Lakkis, Lara1
  • Alhusban, Ala A1
  • Tarawneh, Shahd2
  • Abu-Irmaileh, Bashaer3
  • Albustanji, Sokiyna1
  • Al-Bawab, Abdel Qader1
  • 1 Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan. , (Jordan)
  • 2 Faculty of Science, Mutah University, Karak 61710, Jordan. , (Jordan)
  • 3 Hamdi Mango Center for Scientific Research, The University of Jordan, Amman 11942, Jordan. , (Jordan)
Type
Published Article
Journal
Genes
Publisher
MDPI AG
Publication Date
May 19, 2021
Volume
12
Issue
5
Identifiers
DOI: 10.3390/genes12050777
PMID: 34069745
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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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