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

doi:10.1016/j.canlet.2007.09.009

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 journal › Article › peer-review

25 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 language	English (US)
Pages (from-to)	291-300
Number of pages	10
Journal	Cancer Letters
Volume	258
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2007.09.009
State	Published - Dec 18 2007
Externally published	Yes

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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10.1016/j.canlet.2007.09.009

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@article{539b08d1c9904ed29173cd5f0eb0524f,

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

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.",

keywords = "Cyclooxygenase-2, IRS-1, Insulin-like growth factor-I receptor, Pancreatic cancer, Signaling",

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

note = "Funding Information: Densitometric analysis of autoradiographs was performed with NIH Image Analysis software (V1.62) from the National Institutes of Health (Bethesda, MD) to quantify the results of Northern and Western blot analyses. 3 ",

year = "2007",

month = dec,

day = "18",

doi = "10.1016/j.canlet.2007.09.009",

language = "English (US)",

volume = "258",

pages = "291--300",

journal = "Cancer Letters",

issn = "0304-3835",

publisher = "Elsevier Ireland Ltd",

number = "2",

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TY - JOUR

T1 - Regulation of cyclooxygenase-2 (COX-2) expression in human pancreatic carcinoma cells by the insulin-like growth factor-I receptor (IGF-IR) system

AU - Stoeltzing, Oliver

AU - Liu, Wenbiao

AU - Fan, Fan

AU - Wagner, Christine

AU - Stengel, Kathrin

AU - Somcio, Ray J.

AU - Reinmuth, Niels

AU - Parikh, Alexander A.

AU - Hicklin, Daniel J.

AU - Ellis, Lee M.

N1 - Funding Information: Densitometric analysis of autoradiographs was performed with NIH Image Analysis software (V1.62) from the National Institutes of Health (Bethesda, MD) to quantify the results of Northern and Western blot analyses. 3

PY - 2007/12/18

Y1 - 2007/12/18

N2 - 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.

AB - 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.

KW - Cyclooxygenase-2

KW - IRS-1

KW - Insulin-like growth factor-I receptor

KW - Pancreatic cancer

KW - Signaling

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JO - Cancer Letters

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ER -

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

Abstract

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