NF-κB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells
NF-κB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells
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DOI：
10.1002/pros.20376
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发表时间：
2006-08-01
期刊：
影响因子：
2.8
通讯作者：
Leung, Hing Y.
中科院分区：
文献类型：
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作者：
Armstrong, Kelly;Robson, Craig N.;Leung, Hing Y.
背景成纤维细胞生长因子8（FGF 8）在前列腺癌（CaP）中过度表达，与高级别疾病和降低的存活率相关。用组蛋白去乙酰化酶（HDAC）抑制剂曲古抑菌素A（TSA）研究乙酰化在FGF 8转录调控中的作用。通过基因报告基因测定、RT-PCR和Western印迹法研究FGF 8对TSA的转录应答。还进行了染色质免疫沉淀（ChIP）测定。FGF 8响应TSA处理而上调，沿着NF-κ B转录活性。p65过表达激活FGF 8转录。ChIP检测显示，TSA刺激后，p65被募集到含有推定的NF-κ B结合位点的fgf 8启动子。PI-3 K活性是TSA介导的FGF 8上调所必需的。在前列腺癌细胞中使用TSA处理，证明了PI-3 K活性在介导TSA功能中的需要，并且揭示了NF-κ B在FGF 8表达调节中的新作用。
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.