Source:http://linkedlifedata.com/resource/pubmed/id/10188725
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
In human ovarian carcinomas, the p53 tumor-suppressor gene is frequently mutated. Interleukin-6 (IL-6) in these tumors is known to stimulate tumor-cell proliferation. In order to evaluate the effect of several p53 phenotypes on the IL-6 promoter activity, the human ovarian wild-type (wt)-p53 cell line A2780 was stably transfected with an empty plasmid (CMV) or (m)-175-, m-248- or m-273-p53. Electrophoretic mobility-shift assays revealed differences in activator protein-1 (AP-1) DNA-binding activity in the various clones. The CMV and m-273 clone had comparable amounts of AP-1. The m-175 clone displayed the least and m-248 the most pronounced AP-1 binding. Supershift analysis of AP-1/DNA complexes with antibodies against the AP-1 sub-units, c-Fos, FosB, Fra-1, Fra-2, c-Jun, JunB, and JunD, revealed that the AP-1/DNA complexes in the various clones had different compositions. Fra proteins were basically present only in m-175 and m-248 AP-1. IL-6-promoter activity was evaluated in the presence and absence of the AP-1 binding site which showed that the m-175-transfected clone has a transcriptional suppressing AP-1, whereas the CMV and the m-273 clones have an activating AP-1. Exposure of the p53 clones to tumor-necrosis factor-alpha (TNF-alpha) clearly altered the AP-1/DNA complex composition. IL-6-promoter activity was enhanced by TNF-alpha irrespective of the presence of an AP-1 binding site, while the degree of activation differed in the various clones, being most pronounced in the m-175 and m-248 clones. The results demonstrate that the basic and activated IL-6-promoter activity is differently regulated in the various p53 clones, possibly due to alterations in the AP-1 composition.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
236-42
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10188725-DNA, Complementary,
pubmed-meshheading:10188725-DNA-Binding Proteins,
pubmed-meshheading:10188725-Female,
pubmed-meshheading:10188725-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10188725-Genes, p53,
pubmed-meshheading:10188725-Genetic Code,
pubmed-meshheading:10188725-Humans,
pubmed-meshheading:10188725-Interleukin-6,
pubmed-meshheading:10188725-Ovarian Neoplasms,
pubmed-meshheading:10188725-Phenotype,
pubmed-meshheading:10188725-Promoter Regions, Genetic,
pubmed-meshheading:10188725-Transcription Factor AP-1,
pubmed-meshheading:10188725-Transcription Factors,
pubmed-meshheading:10188725-Transfection,
pubmed-meshheading:10188725-Tumor Cells, Cultured,
pubmed-meshheading:10188725-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Differential regulation of IL-6 promoter activity in a human ovarian-tumor cell line transfected with various p53 mutants: involvement of AP-1.
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pubmed:affiliation |
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
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pubmed:publicationType |
Journal Article,
Comparative Study
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