The proportional hazards analyses revealed that two factors, early age at onset of disease in the proband and multiple affected family members, were important determinants of risk of prostate cancer in these families.
To define the nature of this familial aggregation and to assess whether Mendelian inheritance can explain prostate cancer clustering, proportional hazards and segregation analyses were performed on 691 families ascertained through a single prostate cancer proband. Previous studies have demonstrated familial clustering of prostate cancer. Inhibition of apoptosis may represent a major aspect of the regulatory activity of VEGF on These findings identify theįlk-1/KDR receptor and the PI3-kinase/Akt signal transduction pathway as crucial elements in the processes leading to endothelialĬell survival induced by VEGF. InĬontrast, overexpression of a dominant-negative form of Akt blocked the survival effect of VEGF. Furthermore, a constitutivelyĪctive Akt was sufficient to promote survival of serum-starved endothelial cells in transient transfection experiments. Not detected in response to stimulation with placenta growth factor or an Flt-1-selective VEGF mutant.
VEGF mutant induced phosphorylation of the serine-threonine kinase Akt in a PI3-kinase-dependent manner. Endothelial cells cultured in the presence of VEGF and the Flk-1/KDR-selective (PI3-kinase)-specific inhibitors wortmannin and LY294002. This activity was blocked by the phosphatidylinositol 3′-kinase Survival of serum-starved primary human endothelial cells. In this report we demonstrate that VEGF or a mutant, selectivelyīinding to the Flk-1/KDR receptor, displayed high levels of survival activity, whereas Flt-1-specific ligands failed to promote Of which is the induction of proliferation and differentiation. Vascular endothelial growth factor (VEGF) has been found to have various functions on endothelial cells, the most prominent
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