9-β-d-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells

2004 ◽  
Vol 66 (1) ◽  
pp. 178-186 ◽  
Author(s):  
Jing Fang ◽  
Zongxian Cao ◽  
Yi Charlie Chen ◽  
Eddie Reed ◽  
Bing-Hua Jiang
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Vascular Endothelial ◽  
Hypoxia Inducible Factor 1 ◽  
Endothelial Growth Factor

scholarly journals Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-inducible Factor 1α, HDM2, and p70S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling

2004 ◽  
Vol 279 (44) ◽  
pp. 45643-45651 ◽  
Author(s):  
Heath D. Skinner ◽  
Jenny Z. Zheng ◽  
Jing Fang ◽  
Faton Agani ◽  
Bing-Hua Jiang
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Ovarian Cancer Cells ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) expression is elevated in ovarian and other cancer cells. However, the mechanism that causes the increase in VEGF expression still remains to be elucidated. In this study, we demonstrated that activation of PI3K signaling mediated VEGF protein expression at the transcriptional level through hypoxia-inducible factor 1α (HIF-1α) expression in human ovarian cancer cells. We found that inhibition of PI3K activity by LY294002 decreased VEGF transcriptional activation and that forced expression of AKT completely reversed the inhibitory effect. HDM2 and p70S6K1 are two downstream targets of AKT that mediate growth factor-induced VEGF transcriptional activation and HIF-1α expression. The inhibition of PI3K by LY294002 inhibited p70S6K1 and HDM2 activity in the cells. Forced expression of p70S6K1 or HDM2 reversed LY294002-inhibited VEGF transcriptional activation and HIF-1α expression. This study identifies a potential novel mechanism responsible for increased VEGF expression in ovarian cancer cells. It also indicates the important role of VEGF and HIF-1 in ovarian tumorigenesis and angiogenesis, which is mediated by the PI3K/AKT/HDM2 and AKT/p70S6K1 pathways in ovarian cancer cells.

scholarly journals Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells

2011 ◽  
Vol 130 (3) ◽  
pp. 532-543 ◽  
Author(s):  
Tiera A. Liby ◽  
Perry Spyropoulos ◽  
Haley Buff Lindner ◽  
Juanita Eldridge ◽  
Craig Beeson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Factor Secretion ◽  
Growth Factor Secretion
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