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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2005-11-18
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pubmed:abstractText |
Spleen tyrosine kinase (SYK) is a candidate tumor suppressor gene in breast. Loss of SYK expression in breast tumors as a result of DNA hypermethylation promotes tumor cell proliferation and invasion and predicts shorter survival of breast cancer patients. We previously reported that, in addition to its well-known cytoplasmic localization, the full-length Syk is also present in the nucleus and that Syk nuclear translocation is a rate-limiting step to determine Syk tumor suppressor function. Here, we show that the full-length form of Syk acts as a transcription repressor in the cell nucleus. Ectopic expression of Syk down-regulates the transcription of FRA1 and cyclin D1 oncogenes. This transcription-repressing activity of Syk is associated with its binding to members of the histone deacetylase family. Syk interacts with transcription factor Sp1 at the Sp1 DNA-binding site in the FRA1 promoter to repress Sp1-activated FRA1 transcription. Thus, breast tumorigenesis and progression resulting from the loss of SYK are underscored by the derepression of Sp1-mediated oncogene transcription.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-10374837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-10570957,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-10689303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-10963601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11063932,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11431356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11454707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11489794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11536369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11719224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-11893486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-12086591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-12360277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-12445683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-12477728,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-12907655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-13679379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-1473147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-15184866,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-15217947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-15337524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-15492255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-15557085,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-1826542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-7489405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-7545543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-7791782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-7942638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-8114703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-8143345,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-8336939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-9311776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-9724731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16288017-9819396
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10289-97
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:16288017-Animals,
pubmed-meshheading:16288017-Breast Neoplasms,
pubmed-meshheading:16288017-COS Cells,
pubmed-meshheading:16288017-Cell Line, Tumor,
pubmed-meshheading:16288017-Cercopithecus aethiops,
pubmed-meshheading:16288017-Enzyme Precursors,
pubmed-meshheading:16288017-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16288017-Genes, Tumor Suppressor,
pubmed-meshheading:16288017-Histone Deacetylases,
pubmed-meshheading:16288017-Humans,
pubmed-meshheading:16288017-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16288017-Promoter Regions, Genetic,
pubmed-meshheading:16288017-Protein-Tyrosine Kinases,
pubmed-meshheading:16288017-Repressor Proteins,
pubmed-meshheading:16288017-Transcriptional Activation
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pubmed:year |
2005
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pubmed:articleTitle |
Transcription repressor activity of spleen tyrosine kinase mediates breast tumor suppression.
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pubmed:affiliation |
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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