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. MATERIALS AND 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. CONCLUSION: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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

El Roz A,Bard JM,Valin S,Huvelin JM,Nazih H

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

3783-9

issue

9

eissn

0250-7005

issn

1791-7530

pii

33/9/3783

journal_volume

33

pub_type

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