Different Biological Action of Oleic Acid in ALDH^high and ALDH^low Subpopulations Separated from Ductal Carcinoma <i>In Situ</i> of Breast Cancer

Abstract

<div><p>The mechanisms underlying breast cancer progression of ductal carcinoma in situ <b>(</b>DCIS) associated with fatty acids are largely unknown. In the present study, we compared the action of oleic acid (OA) on two human DCIS cell lines, MCF10DCIS.COM (ER/PR/HER2-negative) and SUM225 (HER2 overexpressed). OA led to a significant increase in proliferation, migration, lipid accumulation and the expression of lipogenic proteins, such as SREBP-1, FAS and ACC-1, in MCF10DCIS.COM cells but not SUM225 cells. The ALDH^high subpopulation analyzed by the ALDEFLUOR assay was approximately 39.2±5.3% of MCF10DCIS.COM cells but was small (3.11±0.9%) in SUM225 cells. We further investigated the different biological action of OA in the distinct ALDH^low and ALDH^high subpopulations of MCF10DCIS.COM cells. OA led to an increase in the expression of ALDH1A1, ALDH1A2 and ALDH1A3 in MCF10DCIS.COM cells. SREBP-1 and ACC-1 were highly expressed in ALDH^high cells relative to ALDH^low cells, whereas FAS was higher in ALDH^low cells. In the presence of OA, ALDH^high cells were more likely to proliferate and migrate and displayed significantly high levels of SREBP-1 and FAS and strong phosphorylation of FAK and AKT relative to ALDH^low cells. This study suggests that OA could be a critical risk factor to promote the proliferation and migration of ALDH^high cells in DCIS, leading to breast cancer progression.</p></div