title: Cholesterol and breast cancer pathophysiology.
abstract: Cholesterol is a risk factor for breast cancer although the mechanisms by which this occurs are not well understood. One hypothesis is that dyslipidemia results in increased cholesterol content in cell membranes, thus impacting upon membrane fluidity and subsequent signaling. In addition, studies demonstrate that the metabolite, 27-hydroxycholesterol (27HC), can function as an estrogen, increasing the proliferation of estrogen receptor (ER)-positive breast cancer cells. This was unexpected because 27HC and other oxysterols activate the liver X receptors (LXR), resulting in a reduction of intracellular cholesterol. Resolution of this paradox will require dissection of the molecular mechanisms by which ER and LXR converge in breast cancer cells. Regardless, the observation that 27HC influences breast cancer provides a rationale for strategies that target cholesterol metabolism.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, IL 61801, USA.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Nelson
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Ching-yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: donald.mcdonnell@duke.edu.
authors.forename: Donald P
authors.initials: DP
authors.lastname: McDonnell
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011960:Receptors, Estrogen; C076996:27-hydroxycholesterol; D002784:Cholesterol