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• W2014385323 abstract "Background The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has become a potential target for the prevention and treatment of breast cancer. However, recent in vitro and in vivo studies have raised the question of whether activation of PPARγ leads to the promotion or reduction of tumor formation. Studies using several cancer cell lines, animal models, and a variety of PPARγ agonists have shown discordant results, including changes in cellular proliferation, differentiation, and apoptosis of cancer cells and tumors. Methods We studied the effects of low-, moderate-, and high-dose treatment of the PPARγ ligands 15-deoxy-Δ 12,14 prostaglandin J 2 (15dPGJ 2 ) and troglitazone (TGZ) on parameters of cell growth, differentiation, and apoptosis in the epithelial breast cancer cell line MDA-MB-231. Results The biologic effects of these compounds depend largely on ligand concentration and the degree of PPARγ activation. For example, low concentrations of 15dPGJ 2 (<2.5 μM) and TGZ (<5 μM) increased cellular proliferation, but concentrations of 15dPGJ 2 >10 μM and of TGZ at 100 μM blocked cell growth. TGZ (100 μM) slowed cell cycle progression, and 15dPGJ 2 (10 μM) caused an S-phase arrest in the cell cycle and induced morphological characteristics consistent with apoptosis. Expression of CD36, a marker of differentiation in these cells, was induced by 2.5 μM 15dPGJ 2 or 5 to 100 μM TGZ. However, higher concentrations of 15dPGJ 2 did not alter CD36 expression. Transcriptional activation studies demonstrated that 15dPGJ 2 is a more potent PPARγ ligand than TGZ. Regardless of the ligand used, though, low transcriptional activation correlated with an increased cellular proliferation, whereas higher levels of activation correlated with cell cycle arrest and apoptosis. Conclusions PPARγ activation induces several important and seemingly opposite changes in neoplastic cells, depending on the magnitude of PPARγ activation. These data may explain, at least in part, some of the discordant results previously reported." @default.
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• W2014385323 date "2001-09-01" @default.
• W2014385323 modified "2023-09-23" @default.
• W2014385323 title "Magnitude of Peroxisome Proliferator-Activated Receptor-γ Activation is Associated with Important and Seemingly opposite Biological Responses in Breast Cancer Cells" @default.
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• W2014385323 doi "https://doi.org/10.2310/6650.2001.33786" @default.
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