Statements in which the resource exists as a subject.
PredicateObject
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