Journal Article

The oxysterol receptor LXR inhibits proliferation of human breast cancer cells

Lise-Lotte Vedin, Sebastian A. Lewandowski, Paolo Parini, Jan-Åke Gustafsson and Knut R. Steffensen

in Carcinogenesis

Volume 30, issue 4, pages 575-579
Published in print April 2009 | ISSN: 0143-3334
Published online January 2009 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/bgp029
The oxysterol receptor LXR inhibits proliferation of human breast cancer cells

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The oxysterol receptors [liver X receptors (LXRα and LXRβ)] regulate cholesterol and lipid biosynthesis and several studies link dysregulation of these metabolic pathways to aberrant cell growth. Here, we show that activation of LXR significantly reduced proliferation in several human breast cancer cells lines. LXR suppressed messenger RNA and/or protein expression of Skp2, cyclin A2, cyclin D1 and estrogen receptor (ER) α, whereas it increased the expression of p53 at the protein level and maintained the retinoblastoma protein in a hypophosphorylated active form. These changes may constitute part of the molecular mechanisms behind the antiproliferative effect of LXR. Furthermore, activation of LXR induced expression of key lipogenic genes including sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase and stearoyl-coenzyme A desaturase 1, leading to increased triglyceride production in MCF7 cells. Small interfering RNA knockdown of SREBP1c, a master regulator of the lipid biosynthesis, did not abolish the antiproliferative effect of LXR in these cells. Combined these studies identify LXRs as both antiproliferative and lipogenic factors in breast cancer cells and indicate that the antiproliferative effect of LXRs is independent of lipid biosynthesis.

Journal Article.  3549 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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