27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology

Science. 2013 Nov 29;342(6162):1094-8. doi: 10.1126/science.1241908.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / blood
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cholestanetriol 26-Monooxygenase / antagonists & inhibitors
  • Cholestanetriol 26-Monooxygenase / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Hydroxycholesterols / antagonists & inhibitors
  • Hydroxycholesterols / blood
  • Hydroxycholesterols / metabolism*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / metabolism*
  • Lung Neoplasms / secondary
  • Mice
  • Tumor Cells, Cultured


  • Hydroxycholesterols
  • 27-hydroxycholesterol
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase

Associated data

  • GEO/GSE35428
  • GEO/GSE46924