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

被引：16

作者：

Armstrong, Kelly ^{[1
]}

Robson, Craig N. ^{[1
]}

Leung, Hing Y. ^{[1
]}

机构：

[1] Newcastle Univ, No Inst Canc Res, Sch Med, Urol Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

来源：

PROSTATE | 2006年 / 66卷 / 11期

基金：

英国医学研究理事会;

关键词：

HDAC; trichostatin A; PI-3K; FGF8; prostate;

D O I：

10.1002/pros.20376

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-kappa B transcriptional activity. Over-expression of p65 activated FGF8 transcription. ChIP assays revealed p65 recruitment to the fgf8 promoter, containing putative NF-kappa B 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-kappa B in the regulation of FGF8 expression is uncovered.

引用

页码：1223 / 1234

页数：12

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