Implication of proteasome in estrogen receptor degradation

被引:112
作者
El Khissiin, A [1 ]
Leclercq, G [1 ]
机构
[1] Inst Jules Bordet, Med Serv, Lab JC Heuson Cancerol Mammaire, B-1000 Brussels, Belgium
关键词
proteasome; lysosome; calpain; estrogen receptor; MCF-7; cell;
D O I
10.1016/S0014-5793(99)00343-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, NH4Cl, and monensin), calpain inhibitors (calpastatin and PD 150606) and proteasome inhibitors (lactacystin and proteasome inhibitor T) were tested to assess this hypothesis. Among all inhibitors tested, lactacystin and proteasome inhibitor I mere 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 [H-3]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. (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:160 / 166
页数:7
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