Artikel
The radiation induced migration of human squamous carcinoma cells is mediated by the PI3K/Akt pathway
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Veröffentlicht: | 24. April 2007 |
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Gliederung
Text
The mechanisms by which low doses of ionizing radiation promote migration in squamous carcinoma cells are poorly understood. Here we investigated the impact of different intracellular pathways on the migration of human squamous carcinoma cells in vitro after experimental radiation. Migration of 3 cell lines treated with 2-8Gy with and without inhibitors of the MAPK and the PI3K/Akt pathways (PD98059, LY294002, Rapamycin) was investigated using an acute wound healing assay. Using this approach we found an intense increase of the number of migrating cells after irradiation. In all cell lines of this study we observed a dose dependent increase of migration. Treatment with PD98059 results in an enhanced migration, whereas inhibition of the PI3K pathway by LY294002 or the downstream inhibitor Rapamycin leads to a decrease of the number of migrating cells. Activation of the pathways was examined by Western analysis using phosphorylation specific antibodies. By Western analysis we observed a pronounced activation of the MAPK pathway after treatment with the PI3K inhibitor LY294002. In contrast, phosphorylation of Akt was increased after blocking MAPK by PD98059 treatment. This effect seems to be mediated by a complex interaction of intracellular signal transduction pathways. The different biological effects of MAPK and PI3K inhibition after irradiation indicate a crosstalk between these two pathways downstream of PI3K.