Affordable Access

Publisher Website

Implication of proteasome in estrogen receptor degradation

Authors
Journal
FEBS Letters
0014-5793
Publisher
Wiley Blackwell (John Wiley & Sons)
Publication Date
Volume
448
Issue
1
Identifiers
DOI: 10.1016/s0014-5793(99)00343-9
Keywords
  • Proteasome
  • Lysosome
  • Calpain
  • Estrogen Receptor
  • Mcf-7 Cell
Disciplines
  • Biology

Abstract

Abstract In MCF-7 breast cancer cells, estradiol (E 2) and pure antiestrogen RU 58668 down-regulate the estrogen receptor (ER). Interestingly, the protein synthesis inhibitor cycloheximide (CHX) abrogated solely the effect of E 2 suggesting a selective difference in the degradation of the receptor induced by estrogenic and antiestrogenic stimulations. A panel of lysosome inhibitors (i.e. bafilomycin, chloroquine, NH 4Cl, and monensin), calpain inhibitors (calpastatin and PD 150606) and proteasome inhibitors (lactacystin and proteasome inhibitor I) were tested to assess this hypothesis. Among all inhibitors tested, lactacystin and proteasome inhibitor I were the sole inhibitors to abrogate the elimination of the receptor induced by both E 2 and RU 58668; this selective effect was also recorded in cells prelabeled with [ 3H]tamoxifen aziridine before exposure to these ligands. Hence, differential sensitivity to CHX seems to be linked to the different mechanisms which target proteins for proteasome-mediated destruction. Moreover, the two tested proteasome inhibitors produced a slight increase of ER concentration in cells not exposed to any ligand, suggesting also the involvement of proteasome in receptor turnover.

There are no comments yet on this publication. Be the first to share your thoughts.