The oxysterol receptors lxrα and lxrβ suppress proliferation in the colon

Lise Lotte Vedin, Jan Ake Gustafsson, Knut R. Steffensen

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The oxysterol receptors LXRα and LXRβ are members of the nuclear receptor family and established transcriptional regulators of lipid metabolism with additional anti-inflammatory functions. Recent investigations have indicated an important role of LXRs in the control of proliferation. Here we further extend this knowledge to human colon cancer cells and proliferation in mouse colon. We show that activation of LXRs leads to a robust cell cycle arrest in colorectal adenocarcinoma cell lines. At the molecular level LXRs control expression of several cell cycle genes including Skp2, c-Myc, CDKs, cyclins, and p15. Furthermore, activation of LXRs causes hypo-phosphorylation of the retinoblastoma (Rb) tumor suppressor protein. Experiments performed in vivo show that the colon structure appears to be intact in LXR null mice. However, LXRαβ-/- mice show a significant increase of proliferation markers in colon compared to wild type mice and administration of the LXR specific agonist, GW3965 significantly reduced expression of proliferation in mouse colon. Taken together, these findings point toward a strong anti-proliferative effect of LXRs in colon revealing the potential of LXR ligands as possible anti cancer agents.

Original languageEnglish (US)
Pages (from-to)835-844
Number of pages10
JournalMolecular Carcinogenesis
Volume52
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Cell cycle
  • Liver X receptors
  • Nuclear receptors
  • Proliferation

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

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