SANİYE KOÇ ADA, YAHYA YOZBATIRAN, KEZBAN UÇAR ÇIFÇI, BURCU YÜCEL
Turkish Journal of Oncology - 2023;38(4):417-424
OBJECTIVE Breast cancer is the most diagnosed cancer in female gender worldwide and the primary cause of cancer deaths. TMEM97 or MAC30 is a transmembrane protein, and it has been shown to be important in cholesterol metabolism. In this study, we aimed to investigate whether TMEM97 expression is related to tamoxifen resistance in breast cancer. METHODS Protein expression was examined through western blotting in the cell lines. TMEM97 expression was silenced using the CRISPR/Cas9 method. To determine the resistance of cell lines to tamoxifen, cells were incubated with different doses of the drug and cell viability was assessed using the CellTiter-Glo luminescent solution. The AmplexRed cholesterol assay was used to determine intracellular cholesterol levels. RESULTS TMEM97 expression was higher in MCF7 cells and more sensitive to tamoxifen. TMEM97 knock-out isogenic cells were determined more resistant to tamoxifen. In addition, total cholesterol level was increased upon tamoxifen in isogenic cell lines at a similar ratio. CONCLUSION In this study, we found that high TMEM97-expressing cells are resistant to tamoxifen. It could be speculated that TMEM97 expression could be an important indicator for tamoxifen sensitivity. Further studies will elucidate the mechanisms behind this association between gene expression and tamoxifen resistance.
