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

Stoeltzing, Oliver and Liu, Wenbiao and Fan, Fan and Wagner, Christine and Stengel, Kathrin and Somcio, Ray J. and Reinmuth, Niels and Parikh, Alexander A. and Hicklin, Daniel J. and Ellis, Lee M. (2007) Regulation of cyclooxygenase-2 (COX-2) expression in human pancreatic carcinoma cells by the insulin-like growth factor-I receptor (IGF-IR) system. CANCER LETTERS, 258 (2). pp. 291-300. ISSN 0304-3835,

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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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: CANCER CELLS; COLON-CANCER; PROSTAGLANDIN E-2; AUTOCRINE LOOP; MESSENGER-RNA; ANTIBODY A12; ANGIOGENESIS; VIVO; METASTASIS; ACTIVATION; cyclooxygenase-2; pancreatic cancer; insulin-like growth factor-I receptor; IRS-1; signaling
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 25 Nov 2020 06:37
Last Modified: 25 Nov 2020 06:37
URI: https://pred.uni-regensburg.de/id/eprint/31801

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