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 gene expression and lactate concentrations in the culture media during tamoxifen resistance development in the MCF-7 cell line, and examined promoter methylation levels. An upregulation of 2.9 times of gene expression was observed around the IC50 concentration of tamoxifen in treated cells, while fluctuation in 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 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 and gene expression were correlated with the increase in lactate concentration in the culture media of treated MCF-7 cells.