title: Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells.
abstract: BACKGROUND
  Maspin, a putative tumor suppressor that is down-regulated in breast and prostate cancer, has been associated with decreased cell motility. Snail transcription factor is a zinc finger protein that is increased in breast cancer and is associated with increased tumor motility and invasion by induction of epithelial-mesenchymal transition (EMT). We investigated the molecular mechanisms by which Snail increases tumor motility and invasion utilizing prostate cancer cells.
  
  
  METHODS
  Expression levels were analyzed by RT-PCR and western blot analyses. Cell motility and invasion assays were performed, while Snail regulation and binding to maspin promoter was analyzed by luciferase reporter and chromatin immunoprecipitation (ChIP) assays.
  
  
  RESULTS
  Snail protein expression was higher in different prostate cancer cells lines as compared to normal prostate epithelial cells, which correlated inversely with maspin expression. Snail overexpression in 22Rv1 prostate cancer cells inhibited maspin expression and led to increased migration and invasion. Knockdown of Snail in DU145 and C4-2 cancer cells resulted in up-regulation of maspin expression, concomitant with decreased migration. Transfection of Snail into 22Rv1 or LNCaP cells inhibited maspin promoter activity, while stable knockdown of Snail in C4-2 cells increased promoter activity. ChIP analysis showed that Snail is recruited to the maspin promoter in 22Rv1 cells.
  
  
  CONCLUSIONS
  Overall, this is the first report showing that Snail can negatively regulate maspin expression by directly repressing maspin promoter activity, leading to increased cell migration and invasion. Therefore, therapeutic targeting of Snail may be useful to re-induce expression of maspin tumor suppressor and prevent prostate cancer tumor progression.
authors.affiliation: Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA.
authors.forename: Corey L
authors.initials: CL
authors.lastname: Neal
authors.forename: Veronica
authors.initials: V
authors.lastname: Henderson
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Smith
authors.forename: Danielle
authors.initials: D
authors.lastname: McKeithen
authors.forename: Tisheeka
authors.initials: T
authors.lastname: Graham
authors.forename: Baohan T
authors.initials: BT
authors.lastname: Vo
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Odero-Marah
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015843:Serpins / Q000235:genetics*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C085344:SERPIN-B5; D015843:Serpins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins