Linked Life Data

19465936

Source:http://linkedlifedata.com/resource/pubmed/id/19465936

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-7-20
pubmed:abstractText
The dioxin/aryl hydrocarbon receptor (AhR) is a transcription factor, which has been attributed a role in human cancerogenesis, cell cycle progression and transforming growth factor-beta (TGF-beta) signaling. As TGF-beta is an important mediator of the malignant phenotype of human gliomas, we studied AhR expression and function in glioma cells. AhR was not only expressed in glioma cells in vitro, but was also detected in human gliomas in vivo by immunohistochemistry, with a predominantly nuclear staining in glioblastomas. The AhR agonist, 3-methylcholanthrene, induced AhR nuclear translocation and upregulated mRNA levels of the AhR target gene, cytochrome P450 1A1 (CYP1A1). Conversely, pharmacological inhibition of AhR using the novel AhR antagonist, CH-223191, or AhR gene silencing using small interfering RNA showed that constitutive AhR activity positively controls TGF-beta1, TGF-beta2 and latent TGF-beta-binding protein-1 protein levels in malignant glioma cells. Moreover, antagonism of AhR reduced clonogenic survival and invasiveness of glioma cells. In contrast, AhR regulates TGF-beta signaling negatively in non-neoplastic astrocytes. Thus, the pathogenesis of glioma formation may involve altered AhR regulation of the TGF-beta/Smad pathway, and AhR may represent a promising target for the treatment of human malignant gliomas and other diseases associated with pathological TGF-beta activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2593-605
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Aryl hydrocarbon receptor inhibition downregulates the TGF-beta/Smad pathway in human glioblastoma cells.
pubmed:affiliation
Laboratory of Molecular Neuro-Oncology, Department of General Neurology and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't