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LDL and free fatty acids increase proliferation and migration of estrogen receptor negative (ER−) MDA‐MB‐231 breast cancer cells: involvement of ACAT1 and MAPK signaling
Author(s) -
Antalis Caryl J,
Buhman Kimberly K
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.727.2
Subject(s) - sterol o acyltransferase , cancer cell , cell growth , estrogen receptor , chemistry , lipid droplet , endocrinology , ldl receptor , medicine , cholesteryl ester , cancer , cholesterol , biochemistry , biology , cancer research , breast cancer , lipoprotein
Cancer cells have a constant need for lipids for membrane construction. This need may be met by de novo biosynthesis or by increased uptake of exogenous lipids. Because biosynthesis requires energy, cells that are able to take up more lipids from the environment may have an advantage. We found that ER− MDA‐MB‐231 breast cancer cells have decreased proliferation and migration when grown in media that has been stripped of lipoproteins. Adding back either LDL or free fatty acids increased both proliferation and migration. Both of these functions were dependent on the ability to form cholesteryl esters (CE) by the enzyme acyl‐CoA:cholesterol acyltransferase 1 (ACAT1), as demonstrated by the fact that inhibition of ACAT1 reduced LDL‐ and fatty acid‐induced proliferation and migration. MDA‐MB‐231 cells expressed high levels of ACAT1 as compared to ER+ MCF‐7 breast cancer cells. MDA‐MB‐231 cells had higher CE concentrations, more cytoplasmic lipid droplets, higher ACAT activity and greater ability to take up LDL compared to ER+ MCF‐7 cells. Inhibition of constitutively activated ERK1/2 by U0126 decreased LDL‐ and fatty acid‐induced proliferation and migration of MDA‐MB‐231 cells, indicating that ACAT1 may be a downstream effector of MAPK signaling in this cell line. These findings may have implications for the effects of dietary fat, obesity or metabolic syndrome in the progression of ER− breast cancer.