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 journalArticlepeer-review

182 Scopus citations


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
Issue number1
StatePublished - 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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