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KMID : 0617220010120010011
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Duksung Bulletin Phamaceutical Sciences
2001 Volume.12 No. 1 p.11 ~ p.16
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A Role of PI3K on H-ras-induced Invasion and Motility
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Abstract
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We have previously shown that H-ras, but N-ras, induces an invasiveness and cell motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype. It has been recently shown that phosphatidylinositol 3-kinase (PI3K) plays an important role on cell migration. In the present study, we wished to investigate the functional role of PI3K in H-ras-induced invasive phenotype and motility in MCF10A cells. The activation of PI3K was examined by detecting phosphorylation of Akt, a downstream molecule of PI3K, by Western blot analysis. We show that phosphorylated Akt level was upregulated both in H-ras MCF10A cells and N-ras MCF10A cells comparing to the parental MCF10A cells while the amount of total Akt was about the same in the parental, H-ras- and n-ras MCF10A cells. The results suggest that activation of PI3K is not sufficient for invasiveness and motility since PI3K is also activated in the N-ras MCF10A cells which have been shown to be non-invasion and non-motile. We then further investigated the functional significance of PI3K activation in invasion and motility by using the known PI3K inhibitors. LY294002 and wortmannin Treatment of LY294002 and wortmannin significantly reduced invasive phenotype and motility of H-ras MCF10A cells, suggesting that activation of PI3K is not sufficient, but may be required for H-ras-induced invasion and motility.
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