16 1 2004 2 hinese Bulletin of Life Sciences Vol. 16, No. 1 Feb., 2004 1004-0374 (2004) 01-0019-05 1 201203 2 200025 (vascular endothelial growth factor, ) (vascular permeability factor, VPF), -A -B - -D -E (placenta growth factor, PLGF) R-1(flt-1) R-2(flk-1/KDR) R-3(flt-4) neuropilin(npr1/ NPR2) / R322.1;R732.2 A Review of relationship between vascular endothelial growth factor family & receptors and tumor angiogenesis HEN Shan 1, JIN Wei 1, MIN Ping 1, LU He 2 (1 Shanghai Institute of Materia Medica, hinese Academy of Sciences, Shanghai 201203, hina; 2 Le pôle francochinois du science du vivant et génomique, Ruijin Hospital, Shanghai 200025, hina) Abstract: Vascular endothelial growth factor () also named vascular permeability factor (VPF), is an important positive regulator for angiogenesis. This is one target of the anticancer research. Discovered members of family include: -A, -B, -, -D, -E and placenta growth factor (PLGF). Receptors of are R-1(flt-1), R-2(flk-1/KDR), R-3(flt-4) and neuropilin(npr1/npr2). Members of this family can selectively promote mitosis of vascular endotheial cells or lymphatic endothelial cells, stimulate endothelial cells to proliferate and induce angiogenesis. They also enhance the permeability of microvessels, help to establish capillary vessels net. This article mainly reviewed the structures, functional characteristics, relationship between and its inhibitors and tumor angiogenesis. Key words: vascular endothelial growth factor; vascular endothelial growth factors receptors; angiogenesis 30 2003-11-03 (1978 ) (1972 ) 1973 (1957 )
20 1 1.1 -A -A 6p21.3 14kb 8 7 34~45kD -A 5 -A 121 145 165 189 206 1 [1] 5 -A 165 6 mrna 167 186 -B 167 -B 186 21kD 32kD -B 167 -B 186 N -B 167 -B 186 -B 167 B 186 -B 167 7 (EM) -A 145 -A 165 -A 121 6 -A 189 -A 206 -B 167 --A 165 -B 167 --A 165 -A -B -A -A [3,4] -B mrna 1.3 - - 4q34 - cdna 419 46.9kD - N -A 4 - -A 3 N - 1 -A 5 [1] - -A -A 1(HIF-1) EGF TGFα/β 1 FGF -A mrna -A Ras -A IL-1α IL-6 -A 1.2 -B -B 11q13 4kb, 7 6 -B 2.4kD 2.0kD - mrna 2.4kD mrna Eichmann [5] - flt-4 PDGF EGF TGF-β - mrna - mrna IL-1β - (TNF) IL-1α - mrna [4,6] 1.4 -D -D Xp22.31 50kb 7 6 cdna 419 354 -D mrna 2.3kb
21 2.8kb -D - - N N -D -D 3 N- - -D - -D c-fos c-fos -D, TGF-α betacelluin(bt) heregulin-β(hrg-β) -D mrna 1.5 -E -E 20kD -A 121 25 flk-1 -A 165 [6] 1.6 PLGF PLGF 2p16-21 46~50kD PLGF-1 PLGF-2 PLGF-2 [6] 2, -A R-1 R-2 7 R-3 - -D -A Neuropilins(NRP1/NRP2) 2 2.1 R-1(flt-1) R-1 (RTK) HIF-1 R-1 -A R-1 PIGF -B flt-1 -A R-1 - A, -A Park [7] R-1 2
22 R-2 -A PGF R-1 -A [8] R-1 Gille R-1 -PI3 R-1 PL-γ c-rasgap(gtpase activating protein) [9] Fong R-1 -A R-1 R-2 -A PI3-Kinase-Akt R-1 2.3 R-3(flt-4) R-3 - R-3 [12] -D R-3 R-1 -A -A R-1 R-1 (MMP9) [10] R-1 PLGF R- 1 R- 1 (HGF) IL-6 R-1 [11] R-3 R-3 R-3 R-3 R-3 R-3 R-3 MAPK RAFTK - -D R-3 SH/Grb2/SOS Ras/MAPK RAFTK 2.2 R-2(KDR/flk-1) R-2 -A flk-1 8.5~9.5 (-A) R-3 R-3 [13] Makinen [14] -D -A, PL-γ PI3 Ras GTP Src -A Raf-Mek-Erk Ras -A R- 2 R-1 2.4 Neuropilin(NRP1/NRP2) -A -A 121 7 Soker NRP1 collapsinsemaphorin R-2 NRP1 NRP1 R-2
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