Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
21802500
DOI
10.1016/j.toxlet.2011.07.011
PII: S0378-4274(11)01433-0
Knihovny.cz E-zdroje
- MeSH
- aparát dělícího vřeténka účinky léků MeSH
- benzopyren toxicita MeSH
- buněčný cyklus účinky léků MeSH
- časové faktory MeSH
- karcinogeny životního prostředí toxicita MeSH
- karcinom metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- mutageny toxicita MeSH
- nádorové buněčné linie MeSH
- nádory prostaty metabolismus MeSH
- oprava DNA účinky léků MeSH
- polychlorované dibenzodioxiny toxicita MeSH
- protein Wnt 5a MeSH
- proteiny Wnt genetika metabolismus MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- receptory aromatických uhlovodíků agonisté MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- replikace DNA účinky léků MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- benzopyren MeSH
- karcinogeny životního prostředí MeSH
- ligandy MeSH
- mutageny MeSH
- polychlorované dibenzodioxiny MeSH
- protein Wnt 5a MeSH
- proteiny Wnt MeSH
- protoonkogenní proteiny MeSH
- receptory aromatických uhlovodíků MeSH
- WNT5A protein, human MeSH Prohlížeč
Carcinogenic polycyclic aromatic hydrocarbons (PAHs) are known as efficient mutagens and ligands of the aryl hydrocarbon receptor (AhR), which has been suggested to play an important role in prostate carcinogenesis. In order to evaluate the complex relationship between the genotoxicity and the AhR-mediated activity of PAHs in prostate cells, we selected benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as model genotoxic and nongenotoxic AhR ligands, respectively, to explore global changes in gene expression in LNCaP cells by microarray analysis. We identified 112 genes that were differentially expressed in cells treated for 24h with BaP, TCDD or both compounds. Our data indicated that the impacts of BaP and TCDD on transcriptome of LNCaP cells significantly overlap, since over 64% of significantly up-regulated genes and 47% of down-regulated genes were similarly affected by both AhR ligands. This suggested that the activation of AhR played a prominent role in the nongenotoxic effects of BaP in the prostate carcinoma cell model LNCaP. Both AhR ligands suppressed expression of genes associated with cell cycle progression, DNA replication, spindle assembly checkpoint or DNA repair, which probably occurred secondary to inhibition of cell cycle progression. In contrast, we identified Wnt5a, an important regulator of prostate cancer progression, to be induced as early as 6h after exposure to both AhR ligands. The AhR ligand-induced Wnt5a upregulation, together with other observed alterations of gene expression, may further contribute to enhanced cell plasticity of prostate carcinoma cells.
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