Linked Life Data

19882709

Source:http://linkedlifedata.com/resource/pubmed/id/19882709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-7-27
pubmed:abstractText
Malignant gliomas persist as a major disease of morbidity and mortality in adult. Differentiation therapy has emerged as a promising candidate modality. However, the mechanism related is unknown. Here, we show that glycogen synthase kinase-3beta (GSK-3beta) is highly expressed and activated during the cholera toxin-induced differentiation in sensitive C6 and U87-MG malignant glioma cells, whereas the GSK-3alpha activity remains stable. GSK-3beta inhibitors or small interfering RNA suppress the induced-differentiation in sensitive C6 cells. Conversely, overexpression of a constitutively active form of human GSK-3beta (pcDNA3-GSK-3beta-S9A) mutant in resistant U251 glioma cells restores their differentiation capabilities. In addition, GSK-3beta triggers cyclin D1 nuclear export and subsequent degradation, which is necessary for differentiation in C6 and U251 glioma cells. Analysis of human glioma tissues further revealed overexpression of active GSK-3beta. These findings suggest that GSK-3beta is a differentiation fate determinant, and shed new lights on the mechanism by which GSK-3beta regulates cyclin D1 degradation and cellular differentiation in gliomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1271-82
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:19882709-Base Sequence, pubmed-meshheading:19882709-Blotting, Western, pubmed-meshheading:19882709-Brain Neoplasms, pubmed-meshheading:19882709-Cell Differentiation, pubmed-meshheading:19882709-Cell Line, Tumor, pubmed-meshheading:19882709-Cholera Toxin, pubmed-meshheading:19882709-DNA Primers, pubmed-meshheading:19882709-Enzyme Activation, pubmed-meshheading:19882709-Enzyme Inhibitors, pubmed-meshheading:19882709-Flow Cytometry, pubmed-meshheading:19882709-Gene Knockdown Techniques, pubmed-meshheading:19882709-Gene Silencing, pubmed-meshheading:19882709-Glioma, pubmed-meshheading:19882709-Glycogen Synthase Kinase 3, pubmed-meshheading:19882709-Humans, pubmed-meshheading:19882709-RNA, Small Interfering, pubmed-meshheading:19882709-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2010
pubmed:articleTitle
Glycogen synthase kinases-3beta controls differentiation of malignant glioma cells.
pubmed:affiliation
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't