Abstract |
This study was performed to prove our hypothesis that the metabolite(s) of polycyclic aromatic hydrocarbons (PAHs) caused the activation or phosphorylation of p53 via DNA damage to suppress the liver X receptor (LXR)-mediated signal transductions as a probably more direct mechanism. We found that LXR-mediated trans-activation was inhibited by 3-methylchoranthrene (MC) and doxorubicin (Dox) in HepG2 cells carrying wild-type p53, but not in Hep3B cells possessing mutant p53. The exogenous expression of wild-type p53 suppressed the LXR-mediated trans-activation in Hep3B cells. The expression of mRNA for ATP binding cassette A1 was suppressed by MC and Dox in HepG2 cells. The protein expression of retinoid X receptor (RXR), a partner of LXR to form a heterodimer, was suppressed by MC and Dox in HepG2 cells.
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Authors | Shunsuke Iwano, Norihito Shibahara, Tetsuya Saito, Tetsuya Kamataki |
Journal | FEBS letters
(FEBS Lett)
Vol. 580
Issue 3
Pg. 890-3
(Feb 06 2006)
ISSN: 0014-5793 [Print] England |
PMID | 16427050
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- DNA-Binding Proteins
- Liver X Receptors
- Orphan Nuclear Receptors
- Receptors, Cytoplasmic and Nuclear
- Retinoid X Receptors
- Tumor Suppressor Protein p53
- Methylcholanthrene
- Doxorubicin
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Topics |
- Antibiotics, Antineoplastic
(metabolism, pharmacology)
- Cell Line, Tumor
- DNA Damage
(drug effects)
- DNA-Binding Proteins
(metabolism)
- Dimerization
- Doxorubicin
(metabolism, pharmacology)
- Gene Expression Regulation, Neoplastic
(drug effects, genetics)
- Humans
- Liver X Receptors
- Methylcholanthrene
(metabolism, pharmacology)
- Mutation
- Orphan Nuclear Receptors
- Phosphorylation
(drug effects)
- Protein Processing, Post-Translational
(drug effects)
- Receptors, Cytoplasmic and Nuclear
(metabolism)
- Retinoid X Receptors
(biosynthesis)
- Signal Transduction
(drug effects)
- Transcriptional Activation
(drug effects)
- Tumor Suppressor Protein p53
(genetics, metabolism)
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