| http://purl.uniprot.org/citations/18031796 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18031796 | http://www.w3.org/2000/01/rdf-schema#comment | "IntroductionStatins have benefits independent of the plasma cholesterol properties among cancer patients and tissue factor (TF)/FVIIa induce PI3-kinase/AKT dependent anti-apoptosis during serum starvation. We analyzed how simvastatin induces apoptosis in human breast cancer cells and the influence of FVIIa and/or FXa on the proposed apoptosis.Materials and methodsMDA-MB-231 cells were serum starved or treated with 5 microM simvastatin and incubated with 10 and 100 nM FVIIa or 5/130 nM FVIIa/FX. RhoA was analyzed by confocal microscopy and caspase-3, nuclear fragmentation, and NFkappaB translocation were measured using the ArrayScan microscope. mRNA for BCL-2, AKT1 and TF were analyzed with RT-PCR or TaqMan. Protein levels and phosphorylation of PKB/AKT were determined by western blotting.Results and conclusionsSimvastatin-induced apoptosis was recorded at 48 h in the MDA-MB-231 cells. Addition of FVIIa to the cells induced PKB/AKT phosphorylation at 24 h and rescued serum-deprived cells from apoptosis. However, in the presence of simvastatin we were unable to report any phosphorylation of PKB/AKT or anti-apoptotic effect mediated by the TF/FVIIa or TF/FVIIa/FXa complexes. This was due to a RhoA-dependent retention of NFkappaB to the cytosol at 12 h which led to a transcriptional down-regulation of the anti-apoptotic protein BCL-2 as well as reduced AKT1 mRNA production at 24 h and thus diminished levels of PKB/AKT protein. A transcriptional down-regulation of TF at 12 h possibly also contributed to the absent anti-apoptotic signaling. These results thereby support a role for simvastatin in cancer treatment and emphasize the importance of PKB/AKT in TF-signaling."xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.thromres.2007.09.017"xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/author | "Siegbahn A."xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/author | "Aberg M."xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/author | "Wickstrom M."xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/name | "Thromb Res"xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/pages | "191-202"xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/title | "Simvastatin induces apoptosis in human breast cancer cells in a NFkappaB-dependent manner and abolishes the anti-apoptotic signaling of TF/FVIIa and TF/FVIIa/FXa."xsd:string |
| http://purl.uniprot.org/citations/18031796 | http://purl.uniprot.org/core/volume | "122"xsd:string |
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