27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.

Journal Article

Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.

Full Text

Duke Authors

Cited Authors

  • Nelson, ER; Wardell, SE; Jasper, JS; Park, S; Suchindran, S; Howe, MK; Carver, NJ; Pillai, RV; Sullivan, PM; Sondhi, V; Umetani, M; Geradts, J; McDonnell, DP

Published Date

  • November 2013

Published In

Volume / Issue

  • 342 / 6162

Start / End Page

  • 1094 - 1098

PubMed ID

  • 24288332

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1241908

Language

  • eng