Role of v-Raf and truncated form RAF1 in the induction of vascular endothelial growth factor and vascularization.
In this work we studied the effect of v-raf and different form RAF on up regulation of VEGF gene expression and angiogenesis. In the experiments the truncated forms of RAF1 gene were transfected into the cells of the established human urothelial line HCV-29, otherwise non-angiogenic. The plasmids coding for mitochondrial targeted dominant active or dominant negative RAF1 (DAM, DNM respectively) were deleted with RAS binding domain. DAM has the ability to phosphorylate BAD whereas DNM cannot phosphorylate BAD. DAM RAF1, similarly to v-raf transfected cells, induced up-regulation of VEGF and caused angiogenic phenotype as studied in vivo. DNM RAF1 transfectants induced VEGF independent angiogenesis.
Malecki
Maciej
M
Department of Cell Biology, Cancer Center, M. Sklodowska-Curie Institute of Oncology, W. K. Roentgen 5, Warsaw, Poland.
Seneta
Magdalena
M
Miloszewska
Joanna
J
Trembacz
Halina
H
Przybyszewska
Malgorzata
M
Janik
Przemyslaw
P
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D001808:Blood Vessels / Q000254:growth & development*; D015153:Blotting, Western; D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D014158:Transcription, Genetic / Q000235:genetics; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019908:Proto-Oncogene Proteins c-raf