title: Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression.
abstract: 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.
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Berna
authors.initials: B
authors.lastname: Uygur
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lijian
authors.initials: L
authors.lastname: Shao
authors.forename: Diana
authors.initials: D
authors.lastname: Romero
authors.forename: Calvin
authors.initials: C
authors.lastname: Vary
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Wen-Shu
authors.initials: WS
authors.lastname: Wu
mesh_terms: 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
chemical_list: D017931:DNA Primers; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D019938:Cyclin D1