Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
|
pubmed:dateCreated |
1997-9-9
|
pubmed:abstractText |
Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappaB has been reported. In the present study, we investigated the possibility that both of these two transcription factors might contribute to the process of tumor promoter-induced transformation. To establish a stable reporter cell system, two reporter genes were stably transfected into a JB6 mouse tumor promotion-sensitive (P+) cell line: a luciferase reporter controlled by a collagenase AP-1 sequence and a chloramphenicol acetyltransferase reporter controlled by an interleukin 6 NF-kappaB sequence. This double-reporter cell line maintained the phenotype of tumor promotion sensitivity and was able to report basal or induced AP-1 and NF-kappaB transactivation. The cytokine tumor promoter tumor necrosis factor (TNF)-alpha transactivated NF-kappaB and AP-1 for both DNA binding and transcriptional activity. Pyrrolidine dithiocarbamate, an antioxidant that acts as an NF-kappaB inhibitor, efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or TNF-alpha induced NF-kappaB as well as AP-1 transactivation and cell transformation, suggesting dependency of transformation on both transcription factors. The AP-1 transrepressing-retinoid SR11302 transrepressed AP-1 and cell transformation when these were TPA induced but not when TNF-alpha induced, indicating different signaling pathways for TNF-alpha and TPA. Supershift electrophoresis mobility shift assay revealed that Jun B and c-Jun were absent from the AP-1/DNA complex following TNF-alpha but present following TPA treatment. Together, these results suggest that both AP-1 and NF-kappaB activation may be required for transformation whether induced by TPA or by TNF, and the differential sensitivity of TPA and TNF-alpha-induced transformation to inhibition by a retinoid might be explained by differences in the composition of the DNA-bound AP-1 complexes.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticarcinogenic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoids,
http://linkedlifedata.com/resource/pubmed/chemical/SR 11302,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/pyrrolidine dithiocarbamic acid
|
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0008-5472
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
57
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
3569-76
|
pubmed:dateRevised |
2008-11-21
|
pubmed:meshHeading |
pubmed-meshheading:9270030-Animals,
pubmed-meshheading:9270030-Anticarcinogenic Agents,
pubmed-meshheading:9270030-Carcinogens,
pubmed-meshheading:9270030-Cell Transformation, Neoplastic,
pubmed-meshheading:9270030-Cells, Cultured,
pubmed-meshheading:9270030-DNA,
pubmed-meshheading:9270030-Genes, Reporter,
pubmed-meshheading:9270030-Mice,
pubmed-meshheading:9270030-NF-kappa B,
pubmed-meshheading:9270030-Pyrrolidines,
pubmed-meshheading:9270030-Retinoids,
pubmed-meshheading:9270030-Tetradecanoylphorbol Acetate,
pubmed-meshheading:9270030-Thiocarbamates,
pubmed-meshheading:9270030-Time Factors,
pubmed-meshheading:9270030-Transcription Factor AP-1,
pubmed-meshheading:9270030-Transcriptional Activation,
pubmed-meshheading:9270030-Transfection,
pubmed-meshheading:9270030-Tumor Necrosis Factor-alpha
|
pubmed:year |
1997
|
pubmed:articleTitle |
Inhibitors of both nuclear factor-kappaB and activator protein-1 activation block the neoplastic transformation response.
|
pubmed:affiliation |
Laboratory of Biochemical Physiology, National Cancer Institute, Frederick Cancer Research and Development Center, NIH, Maryland 21702, USA. lij@ncifcrf.gov
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|