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The oxysterol receptors lxrα and lxrβ suppress proliferation in the colon
Author(s) -
Vedin LiseLotte,
Gustafsson JanÅke,
Steffensen Knut R.
Publication year - 2013
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.21924
Subject(s) - liver x receptor , biology , oxysterol , retinoblastoma protein , cancer research , colorectal cancer , nuclear receptor , cell cycle , cell growth , medicine , endocrinology , microbiology and biotechnology , cholesterol , cancer , cell , transcription factor , biochemistry , gene , genetics
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. Copyright © 2012 Wiley Periodicals, Inc.