Linked Life Data

19671685

Source:http://linkedlifedata.com/resource/pubmed/id/19671685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-8-21
pubmed:abstractText
Here, we show that NF-kappaB-HIF-1 interaction contributed to breast cancer metastatic capacity by means of an incomplete epithelial/mesenchymal transition and influencing migration, as shown in 1833 (human) and 4T1 (mouse) metastatic cells after different stimuli. The 1833 and the transforming growth factor-beta1-exposed 4T1 cells showed both epithelial (E-cadherins) and mesenchymal (N-cadherins and vimentin) markers, and common mechanisms contributed to the retention of certain epithelial characteristics and the control of migration. The complex NF-kappaB-HIF-1 reciprocal regulation and the enhanced c-Jun expression played a functional role in exacerbating the invasiveness of 1833 cells after p50/p65 transfection and of 4T1 cells exposed to transforming growth factor-beta1. Twist expression seemed to exert a permissive role also regulating epithelial/mesenchymal transition markers. After c-Src wild-type (Srcwt) transfection, c-Src-signal transducer overexpression in 1833 cells increased HIF-1 transactivating activity and invasiveness, and changed E-cadherin/N-cadherin ratio versus mesenchymal phenotype. The transcription factor pattern and the motile phenotype of metastatic 1833 cells were influenced by p65-lysine acetylation and HDAC-dependent epigenetic mechanisms, which positively regulated basal NF-kappaB and HIF-1 activities. However, HDAC3 acted as a corepressor of NF-kappaB activity in parental MDA-MB231 cells, thus explaining many differences from the derived 1833 clone, including reduced HIF-1alpha and c-Jun expression. Invasiveness was differently affected by HDAC knockdown in 1833 and MDA-MB231 cells. We suggest that acetylation/deacetylation are critical in establishing the bone-metastatic gene signature of 1833 cells by regulating the activity of NF-kappaB and HIF-1, and further clarify the epigenetic control of transcription factor network in the motile phenotype of 1833 cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1557-3125
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1328-41
pubmed:meshHeading
pubmed-meshheading:19671685-Acetylation, pubmed-meshheading:19671685-Animals, pubmed-meshheading:19671685-Bone Neoplasms, pubmed-meshheading:19671685-Breast Neoplasms, pubmed-meshheading:19671685-Cell Line, Tumor, pubmed-meshheading:19671685-Cell Movement, pubmed-meshheading:19671685-DNA, Neoplasm, pubmed-meshheading:19671685-Disease Models, Animal, pubmed-meshheading:19671685-Female, pubmed-meshheading:19671685-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19671685-Gene Knockdown Techniques, pubmed-meshheading:19671685-Histone Deacetylases, pubmed-meshheading:19671685-Humans, pubmed-meshheading:19671685-Hypoxia-Inducible Factor 1, pubmed-meshheading:19671685-I-kappa B Proteins, pubmed-meshheading:19671685-Mice, pubmed-meshheading:19671685-NF-kappa B, pubmed-meshheading:19671685-Neoplasm Invasiveness, pubmed-meshheading:19671685-Phenotype, pubmed-meshheading:19671685-Protein Binding, pubmed-meshheading:19671685-Proto-Oncogene Proteins c-jun, pubmed-meshheading:19671685-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:19671685-Signal Transduction, pubmed-meshheading:19671685-Transcriptional Activation, pubmed-meshheading:19671685-Transfection, pubmed-meshheading:19671685-Tumor Markers, Biological
pubmed:year
2009
pubmed:articleTitle
NF-kappaB activation, dependent on acetylation/deacetylation, contributes to HIF-1 activity and migration of bone metastatic breast carcinoma cells.
pubmed:affiliation
Dipartimento di Morfologia Umana e Scienze Biomediche Città Studi, University of Milan, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't