Linked Life Data

21502401

Source:http://linkedlifedata.com/resource/pubmed/id/21502401

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-6-2
pubmed:abstractText
Both STAT3 and NF-?B are persistently activated in diverse cancers and promote tumor cell proliferation, survival, angiogenesis, and metastasis through transcriptional activation of multiple common genes. Paradoxically, STAT3 also suppresses many NF-?B-inducible genes involved in innate and adaptive antitumor immunity in spite of elevated levels of NF-?B in tumors. In this study, we show that expression of many NF-?B downstream target genes in tumors depends on STAT3 DNA binding. When STAT3 is elevated in tumor cells and tumor-infiltrating immune cells, persistently activated NF-?B interacts with STAT3 and preferentially binds to genes with STAT3-binding site(s) in promoters. A large number of NF-?B downstream genes associated with oncogenesis and chronic inflammation contain STAT3 DNA-binding site(s). However, in contrast, many genes frequently associated with antitumor immunity lack STAT3 DNA-binding site(s) and can only be activated by NF-?B when STAT3 is inhibited in tumors. The introduction of STAT3 DNA-binding sequences by site-specific mutagenesis in an immunostimulatory gene promoter allows its transcriptional activation by NF-?B in tumor cells. Furthermore, STAT3 facilitates NF-?B binding to genes that are important for tumor growth while inhibiting its binding to Th-1 immunostimulatory genes in growing tumors, including in tumor-infiltrating immune cells. The results of this study provide insight into how some of the oncogenic/inflammatory and Th-1 immunostimulatory genes are differentially regulated in cancer.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3772-80
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:21502401-Animals, pubmed-meshheading:21502401-Binding Sites, pubmed-meshheading:21502401-Cell Growth Processes, pubmed-meshheading:21502401-Cell Line, Tumor, pubmed-meshheading:21502401-Chromatin Immunoprecipitation, pubmed-meshheading:21502401-DNA, Neoplasm, pubmed-meshheading:21502401-Gene Expression Regulation, Neoplastic, pubmed-meshheading:21502401-Humans, pubmed-meshheading:21502401-Melanoma, pubmed-meshheading:21502401-Mice, pubmed-meshheading:21502401-NF-kappa B, pubmed-meshheading:21502401-Promoter Regions, Genetic, pubmed-meshheading:21502401-STAT3 Transcription Factor, pubmed-meshheading:21502401-Signal Transduction, pubmed-meshheading:21502401-Th1 Cells, pubmed-meshheading:21502401-Transcription, Genetic, pubmed-meshheading:21502401-Transcriptional Activation
pubmed:year
2011
pubmed:articleTitle
A requirement of STAT3 DNA binding precludes Th-1 immunostimulatory gene expression by NF-?B in tumors.
pubmed:affiliation
Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural