PMID- 12205045
OWN - NLM
STAT- MEDLINE
DCOM- 20020911
LR  - 20120215
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 16
IP  - 11
DP  - 2002 Sep
TI  - Bcl-2 overexpression in human melanoma cells increases angiogenesis through VEGF 
      mRNA stabilization and HIF-1-mediated transcriptional activity.
PG  - 1453-5
AB  - The aim of this paper was to study the molecular mechanisms by which bcl-2 
      increases hypoxia-induced vascular endothelial growth factor (VEGF) expression. 
      We demonstrated that bcl-2 overexpression in M14 human melanoma cell line 
      enhances hypoxia-induced VEGF mRNA stability and promoter activation. In 
      particular, the half-life of the message was longer in bcl-2 transfectants 
      (approximately 330 min) than in control cells (approximately 180 min). In 
      addition, bcl-2 overexpression increased VEGF promoter activity through the 
      hypoxia-inducible factor-1 (HIF-1) transcription factor. Increased HIF-1a protein 
      expression and DNA binding activity were detected in bcl-2 overexpressing cells 
      compared with control cells. An enhanced functional activity of secreted VEGF was 
      found both in in vitro and in vivo angiogenic assays, and the use of VEGF 
      specific antibodies validated the role of VEGF on bcl-2-induced angiogenesis. 
      Taken together our results indicate that bcl-2 plays an important role in 
      melanoma angiogenesis, and that VEGF mRNA stabilization and HIF-1-mediated 
      transcriptional activity are two important control points in 
      bcl-2/hypoxia-induced VEGF expression.
FAU - Iervolino, Angela
AU  - Iervolino A
AD  - Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
FAU - Trisciuoglio, Daniela
AU  - Trisciuoglio D
FAU - Ribatti, Domenico
AU  - Ribatti D
FAU - Candiloro, Antonio
AU  - Candiloro A
FAU - Biroccio, Annamaria
AU  - Biroccio A
FAU - Zupi, Gabriella
AU  - Zupi G
FAU - Del Bufalo, Donatella
AU  - Del Bufalo D
LA  - eng
PT  - Journal Article
DEP - 20020701
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lymphokines)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Chick Embryo
MH  - DNA-Binding Proteins/*physiology
MH  - Endothelial Growth Factors/*genetics/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Lymphokines/*genetics/metabolism
MH  - Melanoma/blood/*genetics/metabolism
MH  - Models, Biological
MH  - Neovascularization, Pathologic
MH  - Neovascularization, Physiologic
MH  - Nuclear Proteins/*physiology
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism/*physiology
MH  - *RNA Stability
MH  - RNA, Messenger/metabolism
MH  - *Transcription Factors
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2002/09/03 10:00
MHDA- 2002/09/12 10:01
CRDT- 2002/09/03 10:00
PHST- 2002/09/03 10:00 [pubmed]
PHST- 2002/09/12 10:01 [medline]
PHST- 2002/09/03 10:00 [entrez]
AID - 02-0122fje [pii]
AID - 10.1096/fj.02-0122fje [doi]
PST - ppublish
SO  - FASEB J. 2002 Sep;16(11):1453-5. doi: 10.1096/fj.02-0122fje. Epub 2002 Jul 1.