Linked Life Data

18451179

Source:http://linkedlifedata.com/resource/pubmed/id/18451179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-5-2
pubmed:abstractText
The expression of carbonic anhydrase XII (CA12), a gene that encodes a zinc metalloenzyme responsible for acidification of the microenvironment of cancer cells, is highly correlated with estrogen receptor alpha (ER alpha) in human breast tumors. Here, we show that CA12 is robustly regulated by estrogen via ER alpha in breast cancer cells, and that this regulation involves a distal estrogen-responsive enhancer region. Upon the addition of estradiol, ER alpha binds directly to this distal enhancer in vivo, resulting in the recruitment of RNA polymerase II and steroid receptor coactivators SRC-2 and SRC-3, and changes in histone acetylation. Mutagenesis of an imperfect estrogen-responsive element within this enhancer region abolishes estrogen-dependent activity, and chromosome conformation capture and chromatin immunoprecipitation assays show that this distal enhancer communicates with the transcriptional start site of the CA12 gene via intrachromosomal looping upon hormone treatment. This distal enhancer element is observed in the homologous mouse genomic sequence, and the expression of the mouse homologue, Car12, is rapidly and robustly stimulated by estradiol in the mouse uterus in vivo, suggesting that the ER regulation of CA12 is mechanistically and evolutionarily conserved. Our findings highlight the crucial role of ER in the regulation of the CA12 gene, and provide insight into the transcriptional regulatory mechanism that accounts for the strong association of CA12 and ER in human breast cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3505-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18451179-Animals, pubmed-meshheading:18451179-Base Sequence, pubmed-meshheading:18451179-Breast Neoplasms, pubmed-meshheading:18451179-Carbonic Anhydrases, pubmed-meshheading:18451179-Chromatin, pubmed-meshheading:18451179-Enhancer Elements, Genetic, pubmed-meshheading:18451179-Estradiol, pubmed-meshheading:18451179-Estrogen Receptor alpha, pubmed-meshheading:18451179-Female, pubmed-meshheading:18451179-Gene Expression Regulation, Enzymologic, pubmed-meshheading:18451179-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18451179-Humans, pubmed-meshheading:18451179-Luciferases, pubmed-meshheading:18451179-Mice, pubmed-meshheading:18451179-Mice, Inbred C57BL, pubmed-meshheading:18451179-Molecular Sequence Data, pubmed-meshheading:18451179-Response Elements, pubmed-meshheading:18451179-Selective Estrogen Receptor Modulators, pubmed-meshheading:18451179-Sequence Homology, Nucleic Acid, pubmed-meshheading:18451179-Transfection, pubmed-meshheading:18451179-Tumor Cells, Cultured
pubmed:year
2008
pubmed:articleTitle
Estrogen receptor regulation of carbonic anhydrase XII through a distal enhancer in breast cancer.
pubmed:affiliation
Department of Cell and Developmental Biology, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801-3704, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural