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• W2059983642 abstract "Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for eicosanoids that promotes differentiation of human epithelial and mesenchymal cells in vitro and in vivo. PPARγ was proposed as a target for drug-induced differentiation therapy of cancer. Caveolin-1 is a constituent of plasma membrane caveolae in epithelial cells that is often downregulated upon oncogenic transformation. Caveolin-1 has growth-inhibitory activities and its disruption is sufficient to induce transformation in fibroblasts. Herein we have tested the hypothesis that caveolins are transcriptional target genes for PPARγ. In human HT-29 colon carcinoma cells, thiazolidinedione PPARγ ligands increased the levels of caveolin-1 and caveolin-2 proteins two to fivefold in a concentration-dependent manner within 24 h. In human MCF-7 breast adenocarcinoma cells, nonthiazolidinedione PPARγ ligands elevated caveolin-2 protein three to fourfold, while the thiazoli-dinediones were less effective. Caveolin-1 mRNA levels were found to be upregulated by PPARγ ligands already after 3 h in both the cell lines. Ectopic expression of a dominant-negative PPARγ construct attenuated ligand-induced upregulation of caveolins in both HT-29 and HEK-293T cells, indicating that ligand action is mediated by PPARγ. Ligand-treated MCF-7 cells exhibited a differentiated phenotype, as evinced by analysis of cell-specific differentiation markers: protein levels of maspin were elevated and perinuclear lipid droplets accumulated. In contrast, in HT-29 cells, caveolin expression was not correlated with differentiation. Interestingly, PPARγ partially cofractionated in lipid rafts and could be coimmunoprecipitated from cell lysates with caveolin-1, indicating that PPARγ and caveolin-1 may coexist in a complex. Our data indicate that PPARγ participates in the regulation of caveolin gene expression in human carcinoma cells and suggest that caveolin-1 may mediate some of the phenotypic changes induced by this nuclear receptor in cancer cells. These findings may have potentially important functional implications in the context of cancer differentiation therapy and multidrug resistance." @default.
• W2059983642 created "2016-06-24" @default.
• W2059983642 creator A5031758667 @default.
• W2059983642 creator A5060020593 @default.
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• W2059983642 date "2003-06-17" @default.
• W2059983642 modified "2023-10-16" @default.
• W2059983642 title "Peroxisome proliferator-activated receptor-γ upregulates caveolin-1 and caveolin-2 expression in human carcinoma cells" @default.
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• W2059983642 doi "https://doi.org/10.1038/sj.onc.1206625" @default.
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