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High ACAT1 expression in estrogen receptor negative basal-like breast cancer cells is associated with LDL-induced proliferation
Breast Cancer Research and Treatment, 11/04/09
Antalis CJ et al. – A greater ability to take up, store and utilize exogenous cholesterol confers a proliferative advantage to basal-like ER? breast cancer cells. Differences in lipid uptake and storage capability may at least partially explain the differential effect of a low-fat diet on human breast cancer recurrence.
Methods- lipid storage functions were studied in ER? basal-like MDA-MB-231 and MDA-MB-436 breast cancer cell lines
- Both triacylglycerol and cholesteryl ester (CE) concentrations were higher in the ER? cells, but the ability to synthesize CE distinguished the two types of breast cancer cells
- Higher baseline, oleic acid- and LDL-stimulated CE concentrations were found in ER? compared to ER+ cells
- The differences corresponded to greater mRNA and protein levels of acyl-CoA:cholesterol acyltransferase 1 (ACAT1), higher ACAT activity, higher caveolin-1 protein levels, greater LDL uptake, and lower de novo cholesterol synthesis in ER? cells
- Human LDL stimulated proliferation of ER? MDA-MB-231 cells, but had little effect on proliferation of ER+ MCF-7 cells
- The functional significance of these findings was demonstrated by the observation that the ACAT inhibitor CP-113,818 reduced proliferation of breast cancer cells, and specifically reduced LDL-induced proliferation of ER? cells
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