title: Macrophage apolipoprotein E and proliferation of MCF-7 breast cancer cells: role of LXR.
abstract: BACKGROUND
  Apolipoprotein E (APOE), a lipid transport protein that has a key role in the lipoprotein metabolism, is expressed by macrophages under the control of the transcription factor Liver X Receptor (LXR), an oxysterol-activated transcriptional factor involved in cholesterol metabolism. Recent work has shown that LXR agonists may inhibit breast cancer cell proliferation in vitro. We hypothesized that LXR-activated macrophages, and in particular secreted macrophagic APOE, may potentiate the effect of LXR agonists. Our goal was to evaluate the effect of APOE, secreted by THP-1 macrophages under the control of LXR, on MCF-7 cell proliferation, a model of breast cancer.
  
  
  METHODS
  MCF-7 cells were incubated with supernatants from THP-1 cells previously treated with LXR agonists [T0901317 or 22(R)-hydroxycholestrol], or supernatants from THP-1 cells transfected with siRNA against APOE mRNA.
  
  
  RESULTS
  Viability assays and cell death quantification showed that media from LXR-activated macrophages reduced cell proliferation and increased apoptosis of MCF-7 cells. Interestingly, the opposite effects were observed when MCF-7 cells wre treated with media from the siRNA APOE-mediated knock-down model.
  
  
  CONCLUSIONS
  This study highlights the protective role of LXR-activated macrophages against breast cancer growth, and the implication of APOE protein in the anti-proliferative and pro-apoptotic effects observed.
authors.affiliation: Laboratoire de Biochimie, UFR des Sciences Pharmaceutiques, 1 Rue Gaston Veil, 44068, Nantes, France. el-hassane.nazih@univ-nantes.fr.
authors.forename: Ali
authors.initials: A
authors.lastname: El Roz
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bard
authors.forename: Sabine
authors.initials: S
authors.lastname: Valin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Huvelin
authors.forename: Hassan
authors.initials: H
authors.lastname: Nazih
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D017077:Culture Media, Conditioned; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D049690:History, Ancient; D006801:Humans; D000071518:Liver X Receptors; D061986:MCF-7 Cells; D008264:Macrophages / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D017931:DNA Primers; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D034741:RNA, Small Interfering
keywords: ApoE; LXR; MCF-7; MCF-7 cells; THP-1; apoptosis; proliferation