Linked Life Data

21109939

Source:http://linkedlifedata.com/resource/pubmed/id/21109939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-11-26
pubmed:abstractText
We previously demonstrated, using the glioblastoma cell line U87MG as an experimental model, that the adenoviral mediated overexpression of the truncated protein HARP?111-136 inhibits the proliferation of these cells in vitro as well as tumor growth and angiogenesis in vivo. This study focused on identifying the underlying mechanisms for the observed antitumoral effect. The present study demonstrated that HARP?111-136 induced the ATF4/ATF3/CHOP cascade resulting in a strong expression of the proapoptotic protein CHOP, leading to tumor cell apoptosis as demonstrated by PARP cleavage and FACS analysis. siRNA-mediated CHOP gene silencing abolished Ad-HARP?111-136 induced apoptosis. Moreover, Ad-HARP?111-136 increased the expression of the death receptor DR5 and enhanced U87MG cells sensitivity in vitro to TRAIL a DR5 ligand with subsequent activation of caspase 8. Infection of U87MG cells with Ad-HARP?111-136 also enhanced radiation-induced apoptosis. In vivo, the combination of Ad-HARP?111-136 and radiation therapy resulted in a striking inhibition (92%) of the growth of U87MG xenografts, resulting from the potent effect on tumor angiogenesis and tumor cell apoptosis as determined by TUNEL analysis. Taken together, our results indicated that the inhibitor HARP?111-136 sensitized U87MG cells to apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1791-2423
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
179-88
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
HARP?111-136 enhances radiation-induced apoptosis of U87MG glioblastoma by induction of the proapoptotic protein CHOP.
pubmed:affiliation
CNRS, UMR 8121, Vectorologie et Transfert de Gènes, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't