Tamoxifen Suppresses Clusterin Level through Akt Inactivation and Proteasome Degradation in Human Prostate Cancer Cells
- Authors
- Shim, Jae-Ho; Choi, Chang-Su; Lee, Eun-Chang; Kim, Mie Young; Chun, Young-Jin
- Issue Date
- 31-Jan-2009
- Publisher
- KOREAN SOC APPLIED PHARMACOLOGY
- Keywords
- Tamoxifen; Clusterin; Akt; Proteasome
- Citation
- BIOMOLECULES & THERAPEUTICS, v.17, no.1, pp 25 - 31
- Pages
- 7
- Journal Title
- BIOMOLECULES & THERAPEUTICS
- Volume
- 17
- Number
- 1
- Start Page
- 25
- End Page
- 31
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/23349
- DOI
- 10.4062/biomolther.2009.17.1.25
- ISSN
- 1976-9148
2005-4483
- Abstract
- Clusterin is a heterodimeric sulfated glycoprotein and plays a role in many different types of cancer as a cell survival factor and helps cancerous cells to evade stress-induced apoptosis. To investigate whether the regulation of clusterin expression is involved in the mechanism of anticancer agent, we studied the effect of tamoxifen on clusterin expression in human prostate cancer PC-3 cells. Treatment of PC-3 cells with tamoxifen reduced cellular proliferation. Western blot analyses showed that treatment with tamoxifen suppressed clusterin expression in a concentration-dependent manner. Transfection with clusterin siRNA plasmid showed that clusterin is required for PC-3 cell survival. We found that tamoxifen resulted in a rapid decrease in the phosphorylation of Akt on Ser473 leading to prevent kinase activity. Expression of myristoylated Akt prevented tamoxifen-mediated clusterin downregulation. Interestingly, MG132, a well-known proteasome inhibitor also recovered clusterin expression suppressed by tamoxifen. These data indicate that clusterin expression may be regulated by activation of Akt and ubiquitin-proteasome pathway plays an important role in tamoxifen-mediated clusterin suppression.
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