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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#_4 http://www.w3.org/ns/prov#value We reported previously that transcription factor nuclear factor (NF)-kappaB is constitutively activated in human and murine squamous cell carcinomas (SCCs). The role of NF-kappaB in the cumulative changes in gene expression with transformation and progression of the murine SCC Pam 212 and after switching off NF-kappaB by a dominant negative inhibitor kappaB mutant (IkappaBalphaM) was explored by profiling with a 15,000-element cDNA micoarrray. Remarkably, NF-kappaB modulated the expression of 60% of the 308 genes differentially expressed between normal keratinocytes and metastatic SCCs. NF-kappaB directly or indirectly modulated expression of programs of genes functionally linked to proliferation, apoptosis, adhesion, and angiogenesis. Among these, changes in expression of cyclin D1, inhibitor of apoptosis-1, mutant Trp53, and beta-catenin detected with modulation of NF-kappaB by microarray were confirmed by Western and Northern blot. NF-kappaB DNA binding motifs were detected in the promoter of approximately 63% of genes showing increased expression and 33% of the genes showing decreased expression. The ACTACAG motif implicated in the NF-kappaB-dependent down-regulation of mRNA expression of MyoD and Sox9 was detected in the coding portion of about 15% of genes showing increased or decreased expression. Inactivation of NF-kappaB inhibited malignant phenotypic features including proliferation, cell survival, migration, angiogenesis, and tumorigenesis. These results provide evidence that NF-kappaB is an important modulator of gene expression programs that contribute to the malignant phenotype of SCC. http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15374962 http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15374962 http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#_4 http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE#pubinfo http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE http://purl.org/dc/terms/created 2014-07-03T14:30:27.714+02:00 http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAdjDV0QS1zD7sYiYNbCiht-mlGA4nPbZ5iZ3rPRQaNNE http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234