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NF‐κB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells
Author(s) -
Armstrong Kelly,
Robson Craig N.,
Leung Hing Y.
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20376
Subject(s) - fgf8 , trichostatin a , chromatin immunoprecipitation , prostate cancer , cancer research , biology , transcription factor , downregulation and upregulation , histone deacetylase , microbiology and biotechnology , gene expression , cancer , medicine , histone , fibroblast growth factor , promoter , gene , genetics , receptor
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‐κB transcriptional activity. Over‐expression of p65 activated FGF8 transcription. ChIP assays revealed p65 recruitment to the fgf8 promoter, containing putative NF‐κB 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‐κB in the regulation of FGF8 expression is uncovered. Prostate © 2006 Wiley‐Liss, Inc.