Slug regulates Cyclin D1 expression by ubiquitin-proteasome pathway in prostate cancer cells.
OBJECTIVE
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.


CONCLUSIONS
We found that forced expression of Slug inhibited proliferation of prostate cancer cells through downregulation of cyclin D1 expression. And Slug regulates cyclin D1 expression by ubiquitin-proteasome pathway in PCa cells.
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
G X
GX
Ding
J
J
Liu
C C
CC
Feng
H W
HW
Jiang
J F
JF
Xu
Q
Q
Ding
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D010450:Endopeptidases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D025801:Ubiquitin / Q000737:chemistry; D064570:Ubiquitin-Specific Proteases
D007976:Leupeptins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D025801:Ubiquitin; D019938:Cyclin D1; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde