Linked Life Data

19196966

Source:http://linkedlifedata.com/resource/pubmed/id/19196966

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-2-25
pubmed:abstractText
Glioblastoma multiforme (GBM) is a highly lethal brain tumor for which little treatment is available. The epidermal growth factor receptor (EGFR) signaling pathway is thought to play a crucial role in GBM pathogenesis, initiating the early stages of tumor development, sustaining tumor growth, promoting infiltration, and mediating resistance to therapy. The importance of this pathway is highlighted in the fact that EGFR is mutationally activated in over 50% of GBM tumors. Consistent with this, we show here that concomitant activation of wild-type and/or mutant (vIII) EGFR and ablation of Ink4A/Arf and PTEN tumor suppressor gene function in the adult mouse central nervous system generates a fully penetrant, rapid-onset high-grade malignant glioma phenotype with prominent pathological and molecular resemblance to GBM in humans. Studies of the activation of signaling events in these GBM tumor cells revealed notable differences between wild-type and vIII EGFR-expressing cells. We show that wild-type EGF receptor signals through its canonical pathways, whereas tumors arising from expression of mutant EGFR(vIII) do not use these same pathways. Our findings provide critical insights into the role of mutant EGFR signaling function in GBM tumor biology and set the stage for testing of targeted therapeutic agents in the preclinical models described herein.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-11484948, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-11857804, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-15193025, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-15314020, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-1557402, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-16079829, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-16424019, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-16609043, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-16889899, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-17255257, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-17317137, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-17613433, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-17646646, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-17872411, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-18772890, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-2009534, http://linkedlifedata.com/resource/pubmed/commentcorrection/19196966-8620534
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2712-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis.
pubmed:affiliation
Molecular Oncology Research Institute, Department of Neurosurgery, Tufts University School of Medicine, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural