Linked Life Data

15374962

Source:http://linkedlifedata.com/resource/pubmed/id/15374962

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pubmed-article:15374962pubmed:abstractTextWe 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.lld:pubmed
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pubmed-article:15374962pubmed:articleTitleNuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma.lld:pubmed
pubmed-article:15374962pubmed:affiliationHead and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20832-0001, USA.lld:pubmed
pubmed-article:15374962pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:15374962pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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