title: NF-kappaB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells.
abstract: BACKGROUND
  Fibroblast growth factor 8 (FGF8) is over-expressed in prostate cancer (CaP) correlating with high-grade disease and reduced survival. The role of acetylation in transcriptional regulation of FGF8 was investigated using the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA).
  
  
  METHODS
  FGF8 transcriptional response to TSA was investigated by gene reporter assays, RT-PCR, and Western blotting. Chromatin immunoprecipitation (ChIP) assays were also performed.
  
  
  RESULTS
  FGF8 is upregulated in response to TSA treatment along with NF-kappaB transcriptional activity. Over-expression of p65 activated FGF8 transcription. ChIP assays revealed p65 recruitment to the fgf8 promoter, containing putative NF-kappaB binding sites, post TSA stimulation. PI-3K activity is required for TSA mediated FGF8 upregulation.
  
  
  CONCLUSIONS
  Using TSA treatment in prostate cancer cells, a requirement of PI-3K activity in mediating TSA function is demonstrated and a novel role for NF-kappaB in the regulation of FGF8 expression is uncovered.
authors: Urology Research Group, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Medical School, Framlington Place, Newcastle upon Tyne, United Kingdom.
authors: Kelly
authors: K
authors: Armstrong
authors: Craig N
authors: CN
authors: Robson
authors: Hing Y
authors: HY
authors: Leung