Acyl‐CoA:cholesterol acyl transferase (ACAT1) is highly expressed in human breast cancer cell lines and ACAT inhibition reduces proliferation

Abstract

We observed lipid droplets and an increase in cell cholesterol in breast cancer cells treated with fatty acids. We tested these cells for the expression of ACAT1, the enzyme that makes cholesterol esters (CE) from cholesterol and long-chain fatty acids. We found ACAT1 to be highly expressed at both the protein and mRNA levels in the highly proliferative MCF-10A and the invasive MDA-MB-231 breast cancer cell lines. ACAT1 expression was much lower in the estrogen receptor positive (ER+) breast cancer cell line MCF-7 and normal mammary epithelial cells. These data are consistent with existent array data showing increased expression of the ACAT1 gene soat1 in breast cancer compared to normal breast, lower expression in ER+ vs. ER- breast cancer, and co-expression of soat1 with breast cancer proliferation genes. The expression of ACAT1 correlated with CE content and total cell cholesterol. We hypothesized that high ACAT1 expression confers an advantage to proliferating cells when access to lipids needed for growth is limited. To test this hypothesis, we used the ACAT inhibitor CP-113,818. The inhibitor reduced proliferation of the high ACAT1-expressing cells and this effect was more pronounced in low serum media. When LDL was added to the media, it reduced the effect of ACAT inhibition. This suggests that ACAT1 has a role in facilitating growth and may confer a survival advantage to cancer cells when lipids are limited.