Linked Life Data

21596889

Source:http://linkedlifedata.com/resource/pubmed/id/21596889

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-7-8
pubmed:abstractText
Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer, with a survival rate of only 13% to 27% within 2 years of diagnosis despite optimal medical treatment. We hypothesize that the presence of a unique IL-13R?2 decoy receptor prevents GBM apoptosis. This receptor has a high affinity for interleukin-13 (IL-13), binds the cytokine, and competitively inhibits the intracellular signaling cascade initiated by IL-13. In cells lacking the IL-13R?2 decoy receptor, IL-13 initiates the production of 15-lipoxygenase-1 (15-LOX-1), which has been implicated in cellular apoptosis. Our group and others have shown that induction of 15-LOX-1 correlates with tumor cell death in colorectal, pancreatic, and prostate cancer. How 15-LOX-1 induces apoptosis remains unclear. Preliminary evidence in GBM cells implicates an apoptotic process mediated by PPAR?. 15-LOX-1 metabolites can modulate PPAR? and activation of PPAR? can suppress tumor growth. We hypothesize that in GBM, IL-13 can induce 15-LOX-1, which regulates cell apoptosis via signaling through PPAR? and that expression of IL-13R?2 prevents apoptosis and contributes to tumor growth. Our in vitro and in vivo data support this. Knocking down IL-13R?2 with short interfering RNA dramatically induces 15-LOX-1 expression, promotes apoptosis, and reduces GBM tumor growth in vivo. These findings identify a mechanism for eliminating the blockade of endogenous IL-13 signaling and for promotion of apoptosis, and characterize a role for 15-LOX-1 in GBM apoptosis. Identifying a mechanistic pathway that can be targeted for pharmacologic intervention will have applied implications to developing novel and effective treatments of GBM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1538-8514
pubmed:author
pubmed:copyrightInfo
© 2011 American Association for Cancer Research.
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1149-60
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Silencing IL-13R?2 promotes glioblastoma cell death via endogenous signaling.
pubmed:affiliation
Department of Cell Biology, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio 44195, USA. hsil@ccf.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural