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Differential anti-proliferative actions of peroxisome proliferator-activated receptor-gamma agonists in MCF-7 breast cancer cells.

Kim KY, Kim SS, Cheon HG

Bioorganic Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation has been a new approach to cancer therapy. In the present study, we investigated the effects of two structurally different PPARgamma agonists, rosiglitazone and KR-62980 on MCF-7 breast cancer cells. Both agonists inhibited the cell proliferation and colony formation via apoptosis. PTEN expression was increased with decreased Akt phosphorylation by the agonists, whereas agonists actions were abolished in PTEN knockdown cells, indicating the critical role of PTEN in the anti-proliferative effects of PPARgamma activation. Rosiglitazone induced the MCF-7 cell differentiation but KR-62980 did not alter the differentiation pattern with little effects on the lipid accumulation and the expression of lipogenesis markers. These results suggest that PPARgamma activation may result in the inhibition of cell proliferation and/or induction of cell differentiation depending on the type of PPARgamma agonists, and that KR-62980 may be useful in breast cancer therapy by inducing apoptosis.

Published 9 August 2006 in Biochem Pharmacol, 72(5): 530-40.
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