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- W1489631572 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20065182 Increased expression and activation of receptor tyrosine kinases (RTKs) frequently occurs in human brain tumors, mediating a variety of growth-promoting pathways and leading to radioresistance. In this study, we found co-expression of IGF-1R and PDGFR in two glioblastoma (GB) cell lines (18KJ40, 38JL59). Dual targeting of IGF-1R and PDGFR caused synergy in cell death in both 18KJ40 and 38JL59cell lines. In addition, co-inhibition of of IGF-1R and PDGFR incresed radiosensitivity in 18KJ40 cells but failed to intensify the effect of radiation in 38JL59 cells. To dissect which of the radiation-responsive signaling pathways elicited by membrane receptors may be responsable for observed differences, we investigate the phosphoinositide 3-kinase (PI3-K) and MAPK kinases (ERK1/2 and c-Jun-NH2-terminal kinase 1 (JNK1)) pathway. PI3-K and ERK1/2 were expressed in both glioblastoma cell lines while JNK1/3 was expressed only in 18KJ40 cells. Ionizing radiation exposure induced JNK activation in 18KJ40 suggesting that radiation-activated JNK may provide an anti-proliferative signalling, parallel to receptors co-targeting, in this cell line. To test this hypothesis, GB cells were treated with dominant negative JNK1 (dnJNK), a specific inhibitor of JNK and the response to radiation was assayed in presence or absence of receptors co-inhibition. Our results showed that, in each treatment conditions, dnJNK protects 18KJ40 cells against γ-irradiation -induced cell death. As would be expected, dnJNK treatment failed to influence radiation response of the 38JL59 cell line, which did not express JNK. Functionally, we found that dual targeting of IGF-1R and PDGFR caused synergystic cell death in GB cell lines and incresed radiosensitivity in JNK-expressing GB cells but had no effect with γ-irradiation in JNK deficient glioblastoma cells." @default.
- W1489631572 created "2016-06-24" @default.
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- W1489631572 date "2006-04-15" @default.
- W1489631572 modified "2023-10-02" @default.
- W1489631572 title "Co-inhibition of IGF-1R and PDGFR synergistically inhibit proliferation in GB cells and induce radiosensitivity in JNK-expressing glioblastoma cells" @default.
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