Treatment of MCF-7 cells with the peroxisome proliferator-activated receptor (PPAR) γ agonists ciglitazone or 15-deoxy-Δ12,14-prostaglandin J2 resulted in a concentration- and time-dependent decrease of cyclin D1 and estrogen receptor (ER) α proteins, and this was accompanied by decreased cell proliferation and G1-G0S→phase progression. Down-regulation of cyclin D1 and ERα by PPARγ agonists was inhibited in cells cotreated with the proteasome inhibitors MG132 and PSII, but not in cells cotreated with the protease inhibitors calpain II and calpeptin. Moreover, after treatment of MCF-7 cells with 15-deoxy-Δ12,14-prostaglandin J2 and immunoprecipitation with cyclin D1 or ERα antibodies, there was enhanced formation of ubiquitinated cyclin D1 and ERα bands. Thus, PPARγ-induced inhibition of breast cancer cell growth is due, in part, to proteasome-dependent degradation of cyclin D1 (and ERα), and this pathway may be important for other cancer cell lines.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Mar 1 2003|
ASJC Scopus subject areas
- Cancer Research