Regulation of cyclooxygenase-2 (COX-2) expression in human pancreatic carcinoma cells by the insulin-like growth factor-I receptor (IGF-IR) system

Oliver Stoeltzing, Wenbiao Liu, Fan Fan, Christine Wagner, Kathrin Stengel, Ray J. Somcio, Niels Reinmuth, Alexander A. Parikh, Daniel J. Hicklin, Lee M. Ellis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Both the insulin-like growth factor-I receptor (IGF-IR) and cyclooxygenase-2 (COX-2) are frequently overexpressed in pancreatic cancer. We hypothesized that IGF-IR is directly involved in induction of COX-2 and sought to investigate signaling pathways mediating this effect. Pancreatic cancer cells (L3.6pl) were stably transfected with a dominant-negative receptor (IGF-IR DN) construct or empty vector (pcDNA). Cells were stimulated with IGF-I to determine activated signaling intermediates and induction of COX-2. Signaling pathways mediating COX-2 induction were identified using signaling inhibitors. IGF-I up-regulated COX-2 selectively via the MAPK/(Erk-1/2) pathway. In addition, IGF-IR DN cells showed a marked decrease in constitutive COX-2 and a blunted response to IGF-I. Similarly, treatment with an anti-IGF-IR antibody effectively inhibited IGF-IR and MAPK/Erk activation and decreased COX-2 in parental cells. In conclusion, activation of IGF-IR mediates COX-2 expression in human pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalCancer Letters
Volume258
Issue number2
DOIs
StatePublished - Dec 18 2007
Externally publishedYes

Keywords

  • Cyclooxygenase-2
  • IRS-1
  • Insulin-like growth factor-I receptor
  • Pancreatic cancer
  • Signaling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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