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27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.

Publication ,  Journal Article
Nelson, ER; Wardell, SE; Jasper, JS; Park, S; Suchindran, S; Howe, MK; Carver, NJ; Pillai, RV; Sullivan, PM; Sondhi, V; Umetani, M; Geradts, J ...
Published in: Science
November 29, 2013

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.

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Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 29, 2013

Volume

342

Issue

6162

Start / End Page

1094 / 1098

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Mice
  • Lung Neoplasms
  • Hypercholesterolemia
  • Hydroxycholesterols
  • Humans
  • General Science & Technology
  • Female
  • Disease Models, Animal
  • Cholestanetriol 26-Monooxygenase
 

Citation

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Nelson, E. R., Wardell, S. E., Jasper, J. S., Park, S., Suchindran, S., Howe, M. K., … McDonnell, D. P. (2013). 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science, 342(6162), 1094–1098. https://doi.org/10.1126/science.1241908
Nelson, Erik R., Suzanne E. Wardell, Jeff S. Jasper, Sunghee Park, Sunil Suchindran, Matthew K. Howe, Nicole J. Carver, et al. “27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.Science 342, no. 6162 (November 29, 2013): 1094–98. https://doi.org/10.1126/science.1241908.
Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 2013 Nov 29;342(6162):1094–8.
Nelson, Erik R., et al. “27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology.Science, vol. 342, no. 6162, Nov. 2013, pp. 1094–98. Pubmed, doi:10.1126/science.1241908.
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. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 2013 Nov 29;342(6162):1094–1098.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

November 29, 2013

Volume

342

Issue

6162

Start / End Page

1094 / 1098

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Mice
  • Lung Neoplasms
  • Hypercholesterolemia
  • Hydroxycholesterols
  • Humans
  • General Science & Technology
  • Female
  • Disease Models, Animal
  • Cholestanetriol 26-Monooxygenase