The specific role of
dietary fat in
breast cancer progression is unclear, although a
low-fat diet was associated with decreased recurrence of
estrogen receptor alpha negative (ER(-))
breast cancer. ER(-) basal-like MDA-MB-231 and MDA-MB-436
breast cancer cell lines contained a greater number of cytoplasmic lipid droplets compared to
luminal ER(+) MCF-7 cells. Therefore, we studied
lipid storage functions in these cells. 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. Taken together, our studies show that 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.