Estrogen receptor
![]()
(ER
![]()
) plays an important role in the development and progression of breast cancer, and recent studies showed that ER
![]()
expression is associated with resistance to hormonal therapy. Therefore, a number of studies have explored ways to deplete ER
![]()
from breast cancer cells as a new therapy especially for hormone-refractory breast cancer. We reported here that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, effectively depletes ER
![]()
in breast cancer MCF-7 cells. However, the intrinsic mechanisms by which SAHA decreases ER
![]()
levels are not clear. Our present data demonstrated that both inhibition of ER
![]()
mRNA level and promotion of ER
![]()
degradation by the proteasome contribute to SAHA-induced ER
![]()
depletion, indicating that SAHA may exert its effects through transcriptional and posttranslational mechanisms. Furthermore, the decrease of ER
![]()
protein level in MCF-7 cells after SAHA treatment is mainly the result of its rapid degradation by the ubiquitin-proteasome pathway rather than transcriptional inhibition. In addition, we showed that inactivation of the heat shock protein-90 (Hsp90) is involved in SAHA-induced ER
![]()
degradation, and ubiquitin ligase CHIP (C-terminal H
sc70 interacting protein) enhances SAHA-induced ER
![]()
degradation. SAHA-induced ER
![]()
depletion is paralleled with reduction of transcriptional activity of ER
![]()
and SAHA is able to effectively inhibit cell proliferation and induce apoptosis of MCF-7 cells. Taken together, our results revealed a mechanism for SAHA-induced ER
![]()
degradation and indicated that SAHA is a suitable pharmacological agent for depletion of ER
![]()
and a potential choice for breast cancer expressing high ER
![]()
.