PMID- 10585578
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20220318
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 85
IP  - 1
DP  - 2000 Jan 1
TI  - Concomitant over-expression of vascular endothelial growth factor and its 
      receptors in pancreatic cancer.
PG  - 27-34
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic polypeptide that 
      activates 2 distinct high-affinity tyrosine kinase receptors, flk-1/KDR and 
      flt-1. In the present study, we characterized the expression of VEGF and its 
      receptors flk-1/KDR and flt-1 in the normal human pancreas and in human 
      pancreatic cancer tissues and cell lines. VEGF, flk-1/KDR and flt-1 mRNA levels 
      were elevated in cancer tissues compared with normal pancreas. By 
      immuno-histochemistry, VEGF, flk-1/KDR and flt-1 immunoreactivity co-localized in 
      many of the cancer cells within the tumor mass. Three (AsPC-1, Capan-1 and 
      MIAPaCa-2) of 6 pancreatic cancer cell lines expressed flk-1/KDR mRNA and 
      protein, and 4 cell lines (AsPC-1, Capan-1, T3M4 and PANC-1) expressed flt-1 mRNA 
      transcripts. Binding studies with (125)I-labeled VEGF165 indicated that only 
      Capan-1 cells exhibited high levels of specific binding. Furthermore, VEGF 
      enhanced the growth of Capan-1 cells but was without effect in the other cell 
      lines. VEGF also enhanced mitogen-activated protein kinase (MAPK) phosphorylation 
      and c-fos induction in Capan-1 cells, whereas the MAPK kinase inhibitor PD98059 
      abolished the growth-stimulatory effect of VEGF. These data indicate that human 
      pancreatic cancers have the capacity to over-express VEGF and its receptors and 
      suggest that in some instances VEGF may directly promote pancreatic cancer growth 
      via the MAPK pathway.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Itakura, J
AU  - Itakura J
AD  - Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine, 
      Biological Chemistry and Pharmacology, University of California, Irvine, CA, USA.
FAU - Ishiwata, T
AU  - Ishiwata T
FAU - Shen, B
AU  - Shen B
FAU - Kornmann, M
AU  - Kornmann M
FAU - Korc, M
AU  - Korc M
LA  - eng
GR  - CA-40162/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (VEGFA protein, human)
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)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Adenocarcinoma/*metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Blotting, Northern
MH  - Cell Division/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Growth Factors/*biosynthesis/pharmacology
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Lymphokines/*biosynthesis/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Pancreas/cytology/metabolism
MH  - Pancreatic Neoplasms/*metabolism/pathology
MH  - Proto-Oncogene Proteins/*biosynthesis
MH  - Receptor Protein-Tyrosine Kinases/*biosynthesis
MH  - Receptors, Growth Factor/*biosynthesis
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Signal Transduction/drug effects
MH  - Tumor Cells, Cultured
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factor Receptor-1
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1002/(SICI)1097-0215(20000101)85:1<27::AID-IJC5>3.0.CO;2-8 [pii]
AID - 10.1002/(sici)1097-0215(20000101)85:1<27::aid-ijc5>3.0.co;2-8 [doi]
PST - ppublish
SO  - Int J Cancer. 2000 Jan 1;85(1):27-34. doi: 
      10.1002/(sici)1097-0215(20000101)85:1<27::aid-ijc5>3.0.co;2-8.