Induction of Vascular Endothelial Growth Factor by Hypoxia Is Modulated by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Ha-ras-Transformed Cells Through a Hypoxia Inducible Factor-1 Transcriptional Element

摘要: Tumor angiogenesis, the development of new blood vessels, is a highly regulated process that controlled genetically by alterations in oncogene and tumor suppressor gene expression physiologically microenvironment. Previous studies indicate angiogenic switch Ras-transformed cells may be promoted microenvironment through induction mitogen, vascular endothelial growth factor (VEGF). In this report, we show do not use downstream effectors c-Raf-1 or mitogen activated protein kinases (MAPK) signaling VEGF hypoxia as overexpression kinase-defective alleles these genes does inhibit under low oxygen conditions. contrast to c-Raf-1/MAP kinase pathway, increases phosphatidylinositol 3-kinase (PI 3-kinase) activity Ras-dependent manner, inhibition PI pharmacologically results induction. We propose modulates activation stress inducible 3-kinase/Akt pathway factor-1 (HIF-1) transcriptional response element.