Overexpression of vascular endothelial growth factor induces cell transformation in cooperation with fibroblast growth factor 2.
Vascular endothelial growth factor (VEGF) is a family of homodimeric proteins produced from a single gene by alternative splicing of the VEGF transcript. VEGF induces in vivo angiogenesis and vascular permeability. We have recently demonstrated that VEGF is an autocrine growth factor for retinal pigment epithelial (RPE) cells. To further understand the role of VEGF, we overexpressed VEGF in rat RPE cells. The transfected cells exhibited a growth advantage in vitro and an increased response to the mitogenic effect of fibroblasts growth factor-2 (FGF-2), and formed colonies in soft agar upon FGF-2 addition. Moreover, analysis of FGF-receptors evidenced a dramatic increase in FGFR-1 mRNA and protein level, supporting the hypothesis that this receptor mediates the transforming effect of FGF-2. These results reveal that the oncogenic role of VEGF is exerted through a cross regulation between VEGF and FGF signal transduction pathways.
Guerrin
M
M
Laboratoire de Biologie Moléculaire Eucaryote, UPR 9006 Centre National de la Recherche Scientifique, Toulouse, France.
Scotet
E
E
Malecaze
F
F
Houssaint
E
E
Plöuet
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D008222:Lymphokines / Q000096:biosynthesis*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1