Linked Life Data

10416612

Source:http://linkedlifedata.com/resource/pubmed/id/10416612

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1999-8-12
pubmed:abstractText
We demonstrated recently that constitutive expression of proinflammatory cytokines interleukin (IL)-1alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor in head and neck squamous cell carcinoma is correlated with activation of transcription factor nuclear factor (NF)-kappaB/Rel A (p50/p65), which binds the promoter region within each of the genes encoding this repertoire of cytokines. NF-kappaB can be activated after signal-dependent phosphorylation and degradation of inhibitor-kappaBalpha and has been reported to promote cell survival and growth. In the present study, we expressed a phosphorylation site mutant of inhibitor-kappaBalpha (IkappaBalphaM) in head and neck squamous cell carcinoma lines UM-SCC-9, -11B, and -38 to determine the effect of inhibition of NF-kappaB on cytokine expression, cell survival in vitro, and growth in vivo. After transfection with IKBalphaM, only a few UM-SCC-9 clones were obtained that stably expressed the mutant IkappaB, suggesting that expression of a mutant IkappaBalpha may affect survival of the transfected UM-SCC cell lines. After cotransfection of IkappaBalphaM with a Lac-Z reporter, we found that the number of surviving beta-galactosidase-positive cells in the three cell lines was reduced by 70-90% when compared with controls transfected with vector lacking the insert. In UM-SCC-9 cells that stably expressed IkappaBalphaM, inhibition of constitutive and tumor necrosis factor-a induced NF-kappaB activation, and production of all four cytokines was observed. Although UM-SCC-9 IkappaBalphaM-transfected cells proliferated at the same rate as vector-transfected cells in vitro, a significant reduction in growth of tumor xenografts was observed in SCID mice in vivo. The decreased growth of UM-SCC-9 IkappaBalphaM-transfected tumor cells accompanied decreased immunohistochemical detection of the activated form of NF-kappaB in situ. These results provide evidence that NF-KB and IkappaBalpha play an important role in survival, constitutive and inducible expression of proinflammatory cytokines, and growth of squamous cell carcinoma. NF-kappaB could serve as a potential target for therapeutic intervention against cytokine and other immediate-early gene responses that contribute to the survival, growth, and pathogenesis of these cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3468-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10416612-Animals, pubmed-meshheading:10416612-Carcinoma, Squamous Cell, pubmed-meshheading:10416612-Cytokines, pubmed-meshheading:10416612-DNA-Binding Proteins, pubmed-meshheading:10416612-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10416612-Genes, Dominant, pubmed-meshheading:10416612-Genes, Reporter, pubmed-meshheading:10416612-Head and Neck Neoplasms, pubmed-meshheading:10416612-Humans, pubmed-meshheading:10416612-I-kappa B Proteins, pubmed-meshheading:10416612-Lac Operon, pubmed-meshheading:10416612-Mice, pubmed-meshheading:10416612-Mice, SCID, pubmed-meshheading:10416612-NF-kappa B, pubmed-meshheading:10416612-Neoplasm Proteins, pubmed-meshheading:10416612-Neoplasm Transplantation, pubmed-meshheading:10416612-Phosphorylation, pubmed-meshheading:10416612-Point Mutation, pubmed-meshheading:10416612-Promoter Regions, Genetic, pubmed-meshheading:10416612-Protein Processing, Post-Translational, pubmed-meshheading:10416612-Recombinant Fusion Proteins, pubmed-meshheading:10416612-Transcription, Genetic, pubmed-meshheading:10416612-Transfection, pubmed-meshheading:10416612-Tumor Cells, Cultured, pubmed-meshheading:10416612-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo.
pubmed:affiliation
Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.