Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer

Jun Itakura, Toshiyuki Ishiwata, Ben Shen, Marko Kornmann, Murray Korc

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic polypeptide that activates 2 distinct high-affinity tyrosine kinase receptors, flk-I/KDR and flt-I. In the present study, we characterized the expression of VEGF and its receptors flk-I/KDR and fit-I in the normal human pancreas and in human pancreatic cancer tissues and cell lines. VEGF, flk- I/KDR and flt-I mRNA levels were elevated in cancer tissues compared with normal pancreas. By immuno-histochemistry, VEGF, flk-I/KDR and flt-I immunoreactivity co-localized in many of the cancer cells within the tumor mass. Three (AsPC-I, Capan-I and MIAPaCa-2) of 6 pancreatic cancer cell lines expressed flk-I/KDR mRNA and protein, and 4 cell lines (AsPC-I, Capan-I, T3M4 and PANC-I) expressed flt-I mRNA transcripts. Binding studies with 125I- labeled VEGFI65 indicated that only Capan-I cells exhibited high levels of specific binding. Furthermore, VEGF enhanced the growth of Capan-I 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- I 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.

Original languageEnglish (US)
Pages (from-to)27-34
Number of pages8
JournalInternational Journal of Cancer
Volume85
Issue number1
StatePublished - 2000
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Pancreatic Neoplasms
Vascular Endothelial Growth Factor A
Cell Line
Mitogen-Activated Protein Kinases
Messenger RNA
Pancreas
Growth
Neoplasms
Mitogen-Activated Protein Kinase Kinases
Receptor Protein-Tyrosine Kinases
Phosphorylation
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. / Itakura, Jun; Ishiwata, Toshiyuki; Shen, Ben; Kornmann, Marko; Korc, Murray.

In: International Journal of Cancer, Vol. 85, No. 1, 2000, p. 27-34.

Research output: Contribution to journalArticle

Itakura, J, Ishiwata, T, Shen, B, Kornmann, M & Korc, M 2000, 'Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer', International Journal of Cancer, vol. 85, no. 1, pp. 27-34.
Itakura, Jun ; Ishiwata, Toshiyuki ; Shen, Ben ; Kornmann, Marko ; Korc, Murray. / Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. In: International Journal of Cancer. 2000 ; Vol. 85, No. 1. pp. 27-34.
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