Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression.
BACKGROUND
Slug is a transcription factor of the Snail/Slug zinc-finger family and is implicated in metastasis of tumors, but its role in cell proliferation of prostate cancers is unclear.


METHODS
Expression level of Slug and other genes was examined by Western blot, RT-PCR, and QPCR analyses. The forced expression of Slug was mediated by retroviruses and adenoviruses. Slug was downregulated by shRNA. Cell growth was measured by the MTT assay and the quick cell proliferation assay.


RESULTS
Here, we demonstrated that Slug expression is elevated in mouse prostate tumors, and human prostate cancer cell lines LNCaP, PC-3, and 22RV1. Forced expression of Slug-inhibited proliferation of prostate cancer cells PC-3 and DU-145. Conversely, reduced expression of Slug by shRNA promoted growth of PC-3 cancer cells. Consistent with these data, we found that forced expression of Slug in prostate cancer cells led to G1 cell-cycle arrest. Furthermore, ectopic expression of Slug decreased cyclin D1 expression in both PC-3 and DU-145 cells, and knockdown of Slug by shRNA upregulated cyclin D1 expression in these cancer cells. In addition, we demonstrated that ectopic expression of cyclin D1 relieved Slug-mediated inhibition of proliferation of prostate cancer cells.


CONCLUSIONS
We provide the first compelling evidence that Slug is a negative regulator of proliferation of prostate cancer cells. Our findings in this study are distinct from the previously reported role of Slug as a promoter for tumor metastasis, and suggest that Slug is a prognostic marker and potential therapeutic target.
Liu
Jun
J
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
Uygur
Berna
B
Zhang
Zhonghui
Z
Shao
Lijian
L
Romero
Diana
D
Vary
Calvin
C
Ding
Qiang
Q
Wu
Wen-Shu
WS
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D002645:Chickens / Q000276:immunology; D019938:Cyclin D1 / Q000235:genetics*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D019938:Cyclin D1