PPARγ agonists attenuate proliferation and modulate Wnt/β-catenin signalling in melanoma cells

Smith, Aaron G., Beaumont, Kimberley A., Smit, Darren J., Thurber, Amy E., Cook, Anthony L., Boyle, Glen M., Parsons, Peter G., Sturm, Richard A. and Muscat, George E. O. (2009) PPARγ agonists attenuate proliferation and modulate Wnt/β-catenin signalling in melanoma cells. The International Journal of Biochemistry & Cell Biology, 41 4: 844-852. doi:10.1016/j.biocel.2008.08.037


Author Smith, Aaron G.
Beaumont, Kimberley A.
Smit, Darren J.
Thurber, Amy E.
Cook, Anthony L.
Boyle, Glen M.
Parsons, Peter G.
Sturm, Richard A.
Muscat, George E. O.
Title PPARγ agonists attenuate proliferation and modulate Wnt/β-catenin signalling in melanoma cells
Journal name The International Journal of Biochemistry & Cell Biology   Check publisher's open access policy
ISSN 1357-2725
Publication date 2009-04-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.biocel.2008.08.037
Open Access Status
Volume 41
Issue 4
Start page 844
End page 852
Total pages 9
Place of publication U. K.
Publisher Elsevier
Language eng
Subject C1
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
920102 Cancer and Related Disorders
Abstract Peroxisome proliferator-activated receptor-gamma (PPARγ) is a member of the nuclear hormone receptor (NHR) superfamily of ligand-activated transcriptional regulators. Accumulating evidence suggests that PPARγ agonists such as the thiazolidinediones (TZDs) may prove to be useful anti-cancer agents exhibiting anti-proliferative and/or pro-apoptotic affects in a range of cancer cell types including melanoma, however, the mechanisms underlying this effect remain unclear. We have demonstrated the anti-proliferative effects of full and partial PPARγ modulators in human melanoma cell lines. Ablation of PPARγ expression in the MM96L melanoma cell line by siRNA mediated mechanisms attenuates the anti-proliferative effect of these agents suggesting this effect is directly mediated by PPARγ. The mechanisms underlying the anti-proliferative effects of PPARγ in melanoma cells involve the regulation of expression of a number of critical cell cycle genes and β-catenin. Moreover, our data indicate that PPARγ modulates Wnt/β-catenin mediated signalling in melanoma cells in an agonist dependent manner. Abbreviations: MITF, micropthalmia-related transcription factor; Q-RT-PCR, quantitative real-time PCR
Keyword melanoma
PPAR
Beta-catenin
nuclear receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 401716
Institutional Status UQ

 
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Created: Tue, 14 Apr 2009, 21:18:50 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience