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Cancer Res. 2014 Sep 15;74(18):4976-82. doi: 10.1158/0008-5472.CAN-14-1756. Epub 2014 Jul 24.

Obesity, cholesterol metabolism, and breast cancer pathogenesis.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina. donald.mcdonnell@duke.edu.
2
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina.
3
Division of Endocrinology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
4
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Illinois.

Abstract

Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition, significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor in macrophages and possibly other cells, is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. Cancer Res; 74(18); 4976-82.

PMID:
25060521
PMCID:
PMC4167494
DOI:
10.1158/0008-5472.CAN-14-1756
[Indexed for MEDLINE]
Free PMC Article

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