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

共 54 条

[1] Nuclear factor-κ-B:: The enemy within [J].

Aggarwal, BB .

CANCER CELL, 2004, 6 (03) :203-208

[2] The p65 (RelA) subunit of NF-κB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression [J].

Ashburner, BP ;

Westerheide, SD ;

Baldwin, AS .

MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (20) :7065-7077

[3] Tip60 is a nuclear hormone receptor coactivator [J].

Brady, ME ;

Ozanne, DM ;

Gaughan, L ;

Waite, I ;

Cook, S ;

Neal, DE ;

Robson, CN .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) :17599-17604

[4] TRANSCRIPTIONAL SILENCING IN YEAST IS ASSOCIATED WITH REDUCED NUCLEOSOME ACETYLATION [J].

BRAUNSTEIN, M ;

ROSE, AB ;

HOLMES, SG ;

ALLIS, CD ;

BROACH, JR .

GENES & DEVELOPMENT, 1993, 7 (04) :592-604

[5] Histone deacetylase inhibitors stimulate mitochondrial HMG-CoA synthase gene expression via a promoter proximal Sp1 site [J].

Camarero, N ;

Nadal, A ;

Barrero, MJ ;

Haro, D ;

Marrero, PF .

NUCLEIC ACIDS RESEARCH, 2003, 31 (06) :1693-1703

[6] NF-κB activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer [J].

Chen, CD ;

Sawyers, CL .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (08) :2862-2870

[7]

Cohen LA, 2002, ANTICANCER RES, V22, P1497

[8] The Bcl-3 oncoprotein acts as a bridging factor between NF-κB/Rel and nuclear co-regulators [J].

Dechend, R ;

Hirano, F ;

Lehmann, K ;

Heissmeyer, V ;

Ansieau, S ;

Wulczyn, FG ;

Scheidereit, C ;

Leutz, A .

ONCOGENE, 1999, 18 (22) :3316-3323

[9] FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease [J].

Dorkin, TJ ;

Robinson, MC ;

Marsh, C ;

Bjartell, A ;

Neal, DE ;

Leung, HY .

ONCOGENE, 1999, 18 (17) :2755-2761

[10] Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth [J].

Fu, MF ;

Rao, M ;

Wang, CG ;

Sakamaki, T ;

Wang, J ;

Di Vizio, D ;

Zhang, XP ;

Albanese, C ;

Balk, S ;

Chang, CS ;

Fan, SJ ;

Rosen, E ;

Palvimo, JJ ;

Jänne, OA ;

Muratoglu, S ;

Avantaggiati, ML ;

Pestell, RG .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (23) :8563-8575

← 1 2 3 4 5 6 →