Ionizing Radiation Enhances Matrix Metalloproteinase-2 Secretion and Invasion of Glioma Cells through Src/Epidermal Growth Factor Receptor–Mediated p38/Akt and Phosphatidylinositol 3-Kinase/Akt Signaling Pathways

摘要: Glioblastoma is a severe type of primary brain tumor, and its highly invasive character considered to be major therapeutic obstacle. Several recent studies have reported that ionizing radiation (IR) enhances the invasion tumor cells, but mechanisms for this effect are not well understood. In study, we investigated possible signaling involved in IR-induced glioma cells. IR increased matrix metalloproteinase (MMP)-2 promoter activity, mRNA transcription, protein secretion along with invasiveness cells lacking functional PTEN (U87, U251, U373, C6) those harboring wild-type (WT)-PTEN (LN18 LN428). activated phosphatidylinositol 3-kinase (PI3K), Akt, mammalian target rapamycin, blockade these kinases by specific inhibitors (LY294002, Akt inhibitor IV, respectively) transfection dominant-negative (DN) mutants (DN-p85 DN-Akt) or WT-PTEN suppressed MMP-2 U251 U373 addition, epidermal growth factor receptor (EGFR; AG490 AG1478), Src (PP2), p38 (SB203580), EGFR neutralizing antibody, DN-Src DN-p38 significantly blocked phosphorylation secretion. activation was PP2, whereas LY294002 SB203580 did affect activations PI3K, respectively. Finally, kinase reduced on Matrigel. Taken together, our findings suggest induces Src-dependent activation, which triggers p38/Akt PI3K/Akt pathways, leading expression heightened mutant