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Počet príspevkov : 542 Registration date : 18.12.2013
| Predmet: The RT PCRs were per formed in duplicates for four independent experiments and Po február 10, 2014 9:45 am | |
| Activated PI3K phosphorylates phosphatidylinositol 4,5 bisphosphate and generates ARN-509 構造 phosphatidylinosi tol 3,4,5 triphosphate which acts as a second mes senger. Akt interacts with PIP3 and subsequently translocates to the plasma membrane. Akt plays a critical role in controlling the balance between survival and apoptosis. Recent studies indicate that numerous compo nents of the PI3K Akt pathway are targeted by amplifica tion, mutation and translocation more frequently than any other pathway in cancer patients, with resultant acti vation of the pathway, In addition, it has been sug gested that activation of the PI3K Akt pathway is required for the maintenance and viability of cancer stem cells in breast cancer, prostate cancer, and brain tumor, Inhibition of AKT activity in cancer stem cells also resulted in sensitization of cells to therapy and increased survival of mice bearing human glioma xeno grafts in vivo, Hence, the PI3K Akt pathway can be an attractive target for cancer therapy.<br><br> Inhibiting the pathway might also result in differentiation of cancer stem cells, Inhibitor of PI3K internalizes BCRP in stem cells The PI3K Akt pathway can modulate AUY922 構造 functions of ABC transporters through various mechanisms. According to the previous studies, inhibition of the PI3K Akt pathway caused BCRP internalization in cells. Mogi, et al. reported a reduced SP fraction in the bone marrow of Akt1 null mice, Enforced expression of Akt increased the SP fraction in the wild type mouse bone marrow but not in the Bcrp bone marrow.<br><br> They also showed that treatment of SP cells with 10 uM of LY294002 for 90 min promoted Bcrp translocation from the plasma membrane to the intracellular com partment. Similar results have been reported concern ing glioma tumor stem like cells, However, the more detailed molecular mechanism of vesicular BCRP trafficking regulated by the PI3K Akt pathway mostly remains ALK 阻害剤 to be elucidated. Alteration of subcellular BCRP localization was also observed in porcine non SP cells, LLC PK1, Treatment with 20 uM of LY294002 for 90 min caused BCRP internalization from the cell surface. Transfection of the dominant negative Akt plasmid resulted in internalization of a part of BCRP in LLC PK1 cells. Therefore, it was hypothesized that cellular distribution of BCRP might be regulated by the PI3K Akt signaling pathway in non stem cells as well as stem cells.<br><br> LY294002 inhibits BCRP without affecting its translocation However, effects of inhibition of the PI3K Akt pathway in cancer cell lines were different from those in stem cells, In the study, the breast cancer MCF 7 cells were transfected with exogenous BCRP cDNA and MCF 7 BCRP cells that stably overexpress BCRP were established. This cell line expresses epidermal growth factor receptor and may be under the control of its downstream pathways such as the Ras MAPK ERK pathway and the PI3K Akt pathway. | |
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