NF-kappaB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells

Prostate. 2006 Aug 1;66(11):1223-34. doi: 10.1002/pros.20376.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Base Sequence
  • Binding Sites
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatin
  • DNA / chemistry
  • DNA / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 8 / analysis
  • Fibroblast Growth Factor 8 / genetics*
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Histone Deacetylase Inhibitors
  • Humans
  • Hydroxamic Acids / pharmacology
  • Immunosorbent Techniques
  • Male
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic
  • Transfection
  • Up-Regulation

Substances

  • Chromatin
  • Enzyme Inhibitors
  • FGF8 protein, human
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • NF-kappa B
  • RELA protein, human
  • Recombinant Fusion Proteins
  • Transcription Factor RelA
  • Fibroblast Growth Factor 8
  • trichostatin A
  • DNA
  • Phosphatidylinositol 3-Kinases