Troglitazone enhances tamoxifen-induced growth inhibitory activity of MCF-7 cells

Peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands have been identified as a potential source of therapy for human cancers. However, PPAR gamma ligands have a limitation for breast cancer therapy, since estrogen receptor a (ER alpha) negatively interferes with PPAR gamma signaling in breast cancer cells. Here we show that ER alpha inhihits PPAR gamma transactivity and ER alpha-mediated inhibition of PPAR gamma transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ER, with 17-beta-estradiol blocked PPRE transactivity induced by troglitazone, a PPAR gamma ligand, indicating the resistance of ER alpha-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ER alpha-negative MDA-MB-231 cells more than that of ER,positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ER alpha-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ER alpha- positive MCF-7 cells. (C) 2008 Elsevier Inc. All rights reserved