Source:http://linkedlifedata.com/resource/pubmed/id/18337816
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7184
|
| pubmed:dateCreated |
2008-3-13
|
| pubmed:databankReference | |
| pubmed:abstractText |
Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
1476-4687
|
| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
13
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| pubmed:volume |
452
|
| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
187-93
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| pubmed:meshHeading |
pubmed-meshheading:18337816-Animals,
pubmed-meshheading:18337816-Breast Neoplasms,
pubmed-meshheading:18337816-Cell Line,
pubmed-meshheading:18337816-Cell Line, Tumor,
pubmed-meshheading:18337816-Cell Polarity,
pubmed-meshheading:18337816-Disease Progression,
pubmed-meshheading:18337816-Epigenesis, Genetic,
pubmed-meshheading:18337816-Gene Expression Profiling,
pubmed-meshheading:18337816-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18337816-Humans,
pubmed-meshheading:18337816-Lung Neoplasms,
pubmed-meshheading:18337816-Lymphatic Metastasis,
pubmed-meshheading:18337816-Matrix Attachment Region Binding Proteins,
pubmed-meshheading:18337816-Mice,
pubmed-meshheading:18337816-Mice, Nude,
pubmed-meshheading:18337816-Neoplasm Metastasis,
pubmed-meshheading:18337816-Neoplasm Transplantation,
pubmed-meshheading:18337816-Phenotype,
pubmed-meshheading:18337816-Prognosis,
pubmed-meshheading:18337816-RNA Interference,
pubmed-meshheading:18337816-Tumor Markers, Biological
|
| pubmed:year |
2008
|
| pubmed:articleTitle |
SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.
|
| pubmed:affiliation |
Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|