Down-regulation of estrogen receptor-alpha in MCF-7 human breast cancer cells after proteasome inhibition.
The eukaryotic proteasome is a 26S ATP-dependent proteolytic complex, which possesses chymotrypsin-like, trypsin-like and peptidyl glutamyl peptide hydrolase (PGPH) activities, which enable the proteasome to degrade all short-lived and many long-lived proteins, and consequently regulate a myriad of activities in cells. In this study, we observed that inhibition of the proteasome, and more specifically, inhibition of the chymotrypsin-like activity of the proteasome, in MCF-7 human breast cancer cells resulted in selective down-regulation of the nuclear estrogen receptor-alpha (ERalpha). Our data indicated that estrogen had no effect, whereas the ERalpha antagonist, tamoxifen, reduced the amount of ERalpha that could be subjected to down-regulation after proteasome inhibition. Furthermore, our data demonstrated that protein synthesis was required for the down-regulation of ERalpha to occur. Collectively, these data indicate the existence of a proteasome-dependent mechanism that is utilized by MCF-7 cells to maintain a steady-state level of ERalpha.
Balan
Kannan V
KV
Department of Pediatrics, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Suite 3100, Case Western Reserve University, Cleveland, OH 44106, USA.
Wang
Yongbao
Y
Chen
Siming W
SW
Pantazis
Panayotis
P
Wyche
James H
JH
Han
Zhiyong
Z
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D013629:Tamoxifen / Q000494:pharmacology
D047628:Estrogen Receptor alpha; D004967:Estrogens; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D013629:Tamoxifen; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease