Linked Life Data

17568996

Source:http://linkedlifedata.com/resource/pubmed/id/17568996

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-11-13
pubmed:abstractText
Increased expression and activation of receptor tyrosine kinases frequently occur in human brain tumors, mediating a variety of growth-promoting pathways and leading to radioresistance; however, little is known about their motogenic potency relative to one another. In this study, we found co-expression of Insulin like growth factor-1 receptor (IGF-1R) and platelet derived growth factor receptor (PDGFR) in two high-grade gliomas (HGG) cell lines 18 and 38. Dual targeting of IGF-1R and PDGFR increased cell death in both 18 and 38 cell lines in comparison to inhibition of either receptor alone. In addition, co-inhibition of IGF-1R and PDGFR increased radiosensitivity in 18 cells but failed to intensify the effect of radiation in 38 cells. In HGG cells, radiation-induced cell death has been connected to the activation of c-Jun-NH2-terminal kinase-1 (JNK1). We found that JNK1 was weakly expressed in 38 cells while it had an elevated expression in 18 cells. Exposure to ionizing radiation induced JNK1 activation only in 18 cells without affecting the protein activity in 38 cells. These results suggest that in 18 cell line radiation-activated JNK1 may provide an anti-proliferative signaling, parallel to receptors co-targeting. To test this hypothesis, HGG cells were treated with dominant negative JNK1 (dnJNK1) and the response to radiation was assayed in presence or absence of receptors co-inhibition. Indeed dnJNK protected 18 cells against gamma-irradiation-induced cell death. dnJNK treatment did not influence radiation response of the 38 cell line, which expressed low levels of JNK1. In conclusion we found that IGF-1R and PDGFR co-inhibition caused an increased cell death in two HGG cell line and induced the radiosensitization of the JNK1 expressing cell line.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0167-594X
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
245-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17568996-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:17568996-Brain Neoplasms, pubmed-meshheading:17568996-Cell Line, Tumor, pubmed-meshheading:17568996-Cell Proliferation, pubmed-meshheading:17568996-Combined Modality Therapy, pubmed-meshheading:17568996-Drug Combinations, pubmed-meshheading:17568996-Glioma, pubmed-meshheading:17568996-Humans, pubmed-meshheading:17568996-Mitogen-Activated Protein Kinase 8, pubmed-meshheading:17568996-Radiation Dosage, pubmed-meshheading:17568996-Radiation Tolerance, pubmed-meshheading:17568996-Radiation-Sensitizing Agents, pubmed-meshheading:17568996-Receptor, IGF Type 1, pubmed-meshheading:17568996-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:17568996-Second Messenger Systems, pubmed-meshheading:17568996-Signal Transduction, pubmed-meshheading:17568996-Tyrphostins
pubmed:year
2007
pubmed:articleTitle
Dual targeting of IGF-1R and PDGFR inhibits proliferation in high-grade gliomas cells and induces radiosensitivity in JNK-1 expressing cells.
pubmed:affiliation
Department of Oncology-Pathology, Cancer Center Karolinska and Radiumhemmet Karolinska Institute/University Hospital, R8:00, Stockholm 171 76, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't