PMID- 10506722
OWN - NLM
STAT- MEDLINE
DCOM- 19991018
LR  - 20190620
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 86
IP  - 7
DP  - 1999 Oct 1
TI  - KDR activation in astrocytic neoplasms.
PG  - 1335-41
AB  - BACKGROUND: The development of new capillary networks appears to be necessary for
      the growth of solid tumors. Tumor angiogenesis is believed to be mediated by
      soluble factors released from tumor cells that then act on endothelial cells in a
      paracrine manner. Vascular endothelial growth factor (VEGF) is a prime regulator 
      of normal and tumor angiogenesis as well as vasculogenesis. VEGF is expressed in 
      glioma cells and its receptors (Flt-1 and KDR) are expressed in the same gliomas.
      The two receptors are tyrosine kinases and have an extracellular domain
      containing seven immunoglobulin-like loops and a split tyrosine-kinase domain.
      KDR is a receptor for the various VEGF isoforms and for VEGF-C; Flt-1 is a
      receptor for the various isoforms. Studies suggest that the VEGF receptors are
      induced in endothelial cells during tumor angiogenesis. Stimulation of aortic
      endothelial cells results in receptor tyrosine phosphorylation (receptor
      activation). In this study the activation state of the KDR receptors was
      determined in low grade, anaplastic, and high grade gliomas. METHODS: A synthetic
      tyrosine phosphopeptide was used to raise an antibody that recognizes the
      phosphorylation state of tyrosine 1054/1059 in the KDR receptor. Western blot
      analysis was performed on 37 astrocytic neoplasms (7 low grade astrocytomas, 13
      anaplastic astrocytomas, and 17 cases of glioblastoma multiforme). RESULTS:
      Immunoblotting with this antibody found that tyrosines 1054/1059 were
      phosphorylated constitutively within multiple fresh surgical specimens of
      glioblastomas (71%) and anaplastic gliomas (15%), but not in low grade gliomas.
      CONCLUSIONS: The findings of the current study strongly support the hypothesis
      that the onset of angiogenesis is an important event during the disease
      progression of gliomas.
CI  - Copyright 1999 American Cancer Society.
FAU - Carroll, R S
AU  - Carroll RS
AD  - Neurosurgical Laboratories, Brigham and Women's Hospital, Boston, Massachusetts
      02115, USA.
FAU - Zhang, J
AU  - Zhang J
FAU - Bello, L
AU  - Bello L
FAU - Melnick, M B
AU  - Melnick MB
FAU - Maruyama, T
AU  - Maruyama T
FAU - McL Black, P
AU  - McL Black P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antibodies)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - AIM
SB  - IM
MH  - Antibodies
MH  - Astrocytoma/*metabolism/pathology
MH  - Blotting, Western
MH  - Brain Neoplasms/*metabolism/pathology
MH  - Cell Line
MH  - Disease Progression
MH  - Endothelial Growth Factors/*metabolism
MH  - Female
MH  - Glioblastoma/metabolism
MH  - Humans
MH  - Lymphokines/*metabolism
MH  - Male
MH  - Neovascularization, Pathologic
MH  - Phosphorylation
MH  - Protein Isoforms/metabolism
MH  - Receptor Protein-Tyrosine Kinases/immunology/*metabolism
MH  - Receptors, Growth Factor/immunology/*metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - 10.1002/(SICI)1097-0142(19991001)86:7<1335::AID-CNCR32>3.0.CO;2-Z [pii]
AID - 10.1002/(sici)1097-0142(19991001)86:7<1335::aid-cncr32>3.0.co;2-z [doi]
PST - ppublish
SO  - Cancer. 1999 Oct 1;86(7):1335-41. doi:
      10.1002/(sici)1097-0142(19991001)86:7<1335::aid-cncr32>3.0.co;2-z.