Comparative analysis of expression level and activity index of Stearoyl-CoA Desaturase 1 (SCD1) enzyme in breast cancer subtypes

Abstract

Due to the unique conditions of the tumor microenvironment, such as hypoxia, poor angiogenesis and mitochondrial dysfunction, cancer cells face challenges in obtaining nutrients and energy supply. However, monounsaturated fatty acids have been identified as preferred precursors for energy production and maintenance of cellular structures in cancer cells. These fatty acids can be obtained through de novo fatty acid synthesis. Stearoyl-CoA desaturase 1 (SCD1) is the key regulatory enzyme involved in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, and evidence indicates its increased activity in various malignancies, including breast cancer. This study aims to evaluate the expression and activity index of SCD1 in known breast cancer cell lines, including MCF7, SK-BR3 and MDA-MB231, which represent luminal subtypes A and B, HER2 positive and triple negative respectively, as well as tissue samples from affected patients. Materials and methods: Breast cancer cell lines were cultured in RPMI-1640 medium with 10% fetal bovine serum at 37°C, 5% CO2 and 95% humidity for 72 hours. The tissue samples were also immersed in the RNA-later solution and after harvesting the cells and tissue samples, the expression of SCD1 was analyzed using quantitative PCR and the activity index was measured by measuring the ratio of monounsaturated fatty acids to saturated fatty acids using gas liquid chromatography. Results: MCF7 cell line showed higher SCD1 expression compared to MDA-MB231 (250-fold, p-value<0.0001) and SK-BR3 (83-fold, p-value<0.0001) cell lines. SCD1 expression was also higher in luminal tissue samples than HER2 positive (4.9 times, p-value<0.0001) and triple negative (2 times, p-value=0.01). SCD1 activity index in both MCF7 and MDA-MB231 cell lines was 2.10 and 2.09, respectively, and was significantly higher compared to SK-BR3 cell line (1.27, p-value=0.04 for both). Triple negative tissue samples (9.93±4.93) also showed the highest SCD1 activity index compared to luminal samples (3.93 ± 2.4, p-value=0.0002) and HER2 positive samples (5.43 ± 3.44, p-value>0.05).