Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been identified as a potential source of therapy for human cancers. However, PPARγ ligands have a limitation for breast cancer therapy, since estrogen receptor α (ERα) negatively interferes with PPARγ signaling in breast cancer cells. Here we show that ERα inhihits PPARγ transactivity and ERα-mediated inhibition of PPARγ transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ERα with 17-β-estradiol blocked PPRE transactivity induced by troglitazone, a PPARγ ligand, indicating the resistance of ERα-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ERα-negative MDA-MB-231 cells more than that of ERα-positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ERα-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ERα-positive MCF-7 cells.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 5 Dec 2008|
Bibliographical noteFunding Information:
This work was supported in part by research funds from the Chonbuk National University Hospital Research Institute of Clinical Medicine, Korea Breast Cancer Foundation, the Korea Science and Engineering Foundation (M10528010003-05N2801-00310), and a grant of the Post-Doc. Program, Chonbuk National University.
- Breast cancer
- PPARγ ligand