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Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells.
Cancer Res. 63, 958-964 (2003)
Treatment of MCF-7 cells with the peroxisome proliferator-activated receptor (PPAR) gamma agonists ciglitazone or 15-deoxy-Delta 12,14-prostaglandin J2 resulted in a concentration- and time-dependent decrease of cyclin D1 and estrogen receptor (ER) alpha proteins, and this was accompanied by decreased cell proliferation and G(1)-G(0)-->S-phase progression. Down-regulation of cyclin D1 and ER alpha by PPARgamma 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-Delta 12,14-prostaglandin J2 and immunoprecipitation with cyclin D1 or ER alpha antibodies, there was enhanced formation of ubiquitinated cyclin D1 and ER alpha bands. Thus, PPARgamma-induced inhibition of breast cancer cell growth is due, in part, to proteasome-dependent degradation of cyclin D1 (and ER alpha), and this pathway may be important for other cancer cell lines.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2003
HGF-reported in Year
0
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Journal
Cancer Research
Quellenangaben
Volume: 63,
Issue: 5,
Pages: 958-964
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Reviewing status
Peer reviewed
PubMed ID
12615709
Erfassungsdatum
2003-12-31