Impact of Cholesterol and Lipoproteins on Breast Cancer
Epidemiologic evidence indicates a role for cholesterol in breast cancer; however the precise mechanism is unknown. The aberrant regulation of cholesterol homeostasis is often observed in cancer cells, and tumors have increased cholesterol content compared to normal tissue. Cholesterol is a necessary component of cell membranes and serves as a precursor to steroid hormones. We provide further evidence elucidating the role of cholesterol, lipoproteins, and their metabolism in the development of breast cancer. We employ two models of breast cancer to study the effects of cholesterol and lipoproteins on breast cancer. We examine the effects of diet induced hypercholesterolemia on breast cancer development and progression in a murine model of breast cancer. An increase in plasma cholesterol levels, specifically with an increase in high density lipoprotein (HDL) levels, results in larger, more aggressive tumors. Increased HDL levels also effect the expression of proteins involved in lipoprotein metabolism, namely the HDL receptor, scavenger receptor class B, type I (SR-BI.) Further investigation indicates that in human breast cancer cell lines, HDL could stimulate migration and initiate signaling pathways. Decreased expression of SR-BI in these cells results in decreased proliferation, migration, invasion, xenograft tumor growth, and an attenuation of HDL-induced signaling. This work suggests that HDL has pro-oncogenic effects in breast cancer, and identifies a novel potential target, SR-BI, in the treatment of the disease.
Danilo, Christiane, "Impact of Cholesterol and Lipoproteins on Breast Cancer" (2012). ETD Collection for Thomas Jefferson University. AAI3551854.