AIM:Cyclin D1 is an important cell cycle regulatory proteins, which is a functional target of Slug in the regulation of cell growth of prostate cancer cells.
But the pathway of these two factors interacting with each other is unclear.
METHODS:The infectde PCa Cells were treated with proteasome inhibitor MG-132. Expression level of Slug, HA-cyclin D1 and other protein was examined by Western blot.
RESULTS:Increasing doses of adenovirus expressing human Slug were added to DU-145 cells separately, but there were no significantly difference on expressions of Slug and cyclin D1. We found that the protein expressions of HA-Cyclin D1 (wide-type) were all reduced through high expression of Slug, which is dose-dependent. However, there is no change for HA-Cyclin D1 (mutant) expression in PC-3 with pMIGW-Cyclin D1-HA T286A. The protein expression of HA-Cyclin D1 were all reduced three days after infection by adding adenovirus expressing human Slug to PC-3 carrying pMIGW-Cyclin D1-HA vector compared to negative control, which is dose-dependent. However, there is no change for HA-Cyclin D1 expression in PC-3 with pMIGW-Cyclin D1-HA treated by MG-132.
CONCLUSION: We found that forced expression of Slug inhibited proliferation of prostate cancer cells through downregulation of cyclin D1 expression. And Slug regulates cyclin D1 expressionin by ubiquitin-proteasome pathway in PCa cells.
Written by:
Ding GX, Liu J, Feng CC, Jiang HW, Xu JF, Ding Q. Are you the author?
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Reference: Panminerva Med. 2012 Sep;54(3):219-23.
PubMed Abstract
PMID: 22801439
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