Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8325930 | The International Journal of Biochemistry & Cell Biology | 2009 | 9 Pages |
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.
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Authors
Aaron G. Smith, Kimberley A. Beaumont, Darren J. Smit, Amy E. Thurber, Anthony L. Cook, Glen M. Boyle, Peter G. Parsons, Richard A. Sturm, George E.O. Muscat,