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Titolo:
2,4,4 '-trichlorobiphenyl increases STAT5 transcriptional activity
Autore:
Oakley, GG; Roe, AL; Blouin, RA; Twaroski, TP; Ganguly, TC; Vore, M; Lehmler, HJ; Robertson, LW;
Indirizzi:
Univ Kentucky, Med Ctr, Grad Ctr Toxicol, Lexington, KY 40536 USA Univ Kentucky Lexington KY USA 40536 Ctr Toxicol, Lexington, KY 40536 USA Univ Kentucky, Coll Pharm, Chandler Med Ctr, Lexington, KY USA Univ Kentucky Lexington KY USA harm, Chandler Med Ctr, Lexington, KY USA
Titolo Testata:
MOLECULAR CARCINOGENESIS
fascicolo: 4, volume: 30, anno: 2001,
pagine: 199 - 208
SICI:
0899-1987(200104)30:4<199:2'ISTA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYCHLORINATED-BIPHENYLS; CELL-PROLIFERATION; SIGNAL-TRANSDUCTION; ACTIVATOR PROTEIN-1; TUMOR PROMOTION; DNA-BINDING; KAPPA-B; AP-1; PHOSPHORYLATION; DIFFERENTIATION;
Keywords:
tumor promotion; nuclear proteins; DNA binding;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Robertson, LW Univ Kentucky, Med Ctr, Grad Ctr Toxicol, 306 Hlth Sci Res Blgd, Lexington, KY 40536 USA Univ Kentucky 306 Hlth Sci Res Blgd Lexington KY USA 40536 A
Citazione:
G.G. Oakley et al., "2,4,4 '-trichlorobiphenyl increases STAT5 transcriptional activity", MOL CARCINO, 30(4), 2001, pp. 199-208

Abstract

The promoting effects of polychlorinated biphenyls (PCBs) have been studied extensively in a variety of two-stage carcinogenesis models. However, themolecular mechanisms responsible for the promotion effects of PCBs have not been elucidated. We measured the effect of PCBs on DNA-binding proteins involved in cell proliferation and transformation. Male Sprague-Dawley rats were injected intraperitoneally with mono-, di-, tri-, tetra-, or hexachlorobiphenyls (300 mu mol/kg/d) each day for 4 d and killed 4 h after the lastinjection. To detect alterations in nuclear proteins that could explain the tumor-promoter. activity of PCBs, liver nuclear extracts were analyzed byelectrophoretic mobility shift assays. Electrophoretic mobility shift assay analysis of signal transducers and activators of transcription (STAT)-binding activity to a consensus gamma -interferon-activated sequence (GAS) element was compared in liver nuclear extracts from treated rats. STAT-bindingactivity was eightfold to tenfold higher in nuclear extracts from animals treated with 2,4,4 ' -trichloro- (PCB 28) and 2,2 ' ,4,4 ' ,5,5 ' -hexachlorobiphenyl (PCB 153). Analysis of the protein complex binding to the GAS element, with antibodies specific for STAT3, STAT5, and STAT6, indicated thatthe protein complex was made up of STAT5 and STAT6 proteins. HepG2 cells transiently transfected with a luciferase reporter gene construct containingmany STAT5 binding sites were treated with PCB 28 and PCB 153. PCB 28 stimulated a greater than 25-fold increase in luciferase activity at the highest concentration tested, 1.0 mug/mL. However, enhanced luciferase activity did not occur with PCB 153 treatment. 4-Chlorobiphenyl (PCB 3), PCB 28, and PCB 153 treatment of Sprague-Dawley rats resulted in a large increase in protein binding to a consensus activated protein-1 (AP-1) element. However, 3,4-dichlorobiphenyl (PCB 12) and 3,3',4,4'-tetrachlorobiphenyl (PCB 77) treatments did not increase AP-1 transcription activity. Further analysis of the proteins binding to the AP-1 consensus sequence with antibodies specificfor c-fos, junD, and junB indicated that the protein composition consists of junD proteins. These data showed functional differences between noncoplanar and coplanar PCBs with respect to STAT activation and AP-1-DNA binding. (C) 2001 Wiley-Liss, Inc.

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Documento generato il 01/12/20 alle ore 07:50:46