PMID- 15987743
OWN - NLM
STAT- MEDLINE
DCOM- 20060103
LR  - 20220321
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 16
IP  - 9
DP  - 2005 Sep
TI  - Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial 
      growth factor expression in melanoma cells.
PG  - 4153-62
AB  - 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.
FAU - Trisciuoglio, Daniela
AU  - Trisciuoglio D
AD  - Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, 00158 Rome, 
      Italy.
FAU - Iervolino, Angela
AU  - Iervolino A
FAU - Zupi, Gabriella
AU  - Zupi G
FAU - Del Bufalo, Donatella
AU  - Del Bufalo D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050629
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Apoptosis/physiology
MH  - Cell Line, Tumor
MH  - DNA/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Gene Expression Regulation, Neoplastic/physiology
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects/genetics/*physiology
MH  - Melanoma/*enzymology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-bcl-2/*physiology
MH  - RNA Interference
MH  - RNA, Messenger/metabolism
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
PMC - PMC1196326
EDAT- 2005/07/01 09:00
MHDA- 2006/01/04 09:00
PMCR- 2005/10/31
CRDT- 2005/07/01 09:00
PHST- 2005/07/01 09:00 [pubmed]
PHST- 2006/01/04 09:00 [medline]
PHST- 2005/07/01 09:00 [entrez]
PHST- 2005/10/31 00:00 [pmc-release]
AID - E04-12-1087 [pii]
AID - 00164153 [pii]
AID - 10.1091/mbc.e04-12-1087 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2005 Sep;16(9):4153-62. doi: 10.1091/mbc.e04-12-1087. Epub 2005 
      Jun 29.