Gene interactions and pathways from curated databases and text-mining
Mol Biol Cell 2005, PMID: 15987743

Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial growth factor expression in melanoma cells.

Trisciuoglio, Daniela; Iervolino, Angela; Zupi, Gabriella; Del Bufalo, Donatella

We have previously demonstrated that bcl-2 overexpression in tumor cells exposed to hypoxia increases the expression of vascular endothelial growth factor (VEGF) gene through the hypoxia-inducible factor-1 (HIF-1). In this article, we demonstrate that exposure of bcl-2 overexpressing melanoma cells to hypoxia induced phosphorylation of AKT and extracellular signal-regulated kinase (ERK)1/2 proteins. On the contrary, no modulation of these pathways by bcl-2 was observed under normoxic conditions. When HIF-1alpha expression was reduced by RNA interference, AKT and ERK1/2 phosphorylation were still induced by bcl-2. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia. No differences were observed between control and bcl-2-overexpressing cells in normoxia, in terms of VEGF protein secretion and in response to PI3K and MAPK inhibitors. We also demonstrated that RNA interference-mediated down-regulation of bcl-2 expression resulted in a decrease in the ERK1/2 phosphorylation and VEGF secretion only in bcl-2-overexpressing cell exposed to hypoxia but not in control cells. In conclusion, our results indicate, for the first time, that bcl-2 synergizes with hypoxia to promote expression of angiogenesis factors in melanoma cells through both PI3K- and MAPK-dependent pathways.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System, Melanoma
Document information provided by NCBI PubMed

Text Mining Data

vascular endothelial growth factor — MAPK: " Involvement of PI3K and MAPK signaling in bcl-2 induced vascular endothelial growth factor expression in melanoma cells "

vascular endothelial growth factor — PI3K: " Involvement of PI3K and MAPK signaling in bcl-2 induced vascular endothelial growth factor expression in melanoma cells "

VEGF → mitogen activated protein kinase: " Pharmacological inhibition of mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia "

VEGF → phosphatidylinositol 3-kinase (PI3K): " Pharmacological inhibition of mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia "

HIF-1 → mitogen activated protein kinase: " Pharmacological inhibition of mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia "

HIF-1 → phosphatidylinositol 3-kinase (PI3K): " Pharmacological inhibition of mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3-kinase (PI3K) signaling pathways reduced the induction of VEGF and HIF-1 in response to bcl-2 overexpression in hypoxia "

Manually curated Databases

No curated data.