EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF

Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibrobla...

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Main Authors: Panagiotis A. Konstantinopoulos, Gerasimos P. Vandoros, Michalis V. Karamouzis, Maria Gkermpesi, Georgia Sotiropoulou-Bonikou, Athanasios G. Papavassiliou
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2007/831416
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author Panagiotis A. Konstantinopoulos
Gerasimos P. Vandoros
Michalis V. Karamouzis
Maria Gkermpesi
Georgia Sotiropoulou-Bonikou
Athanasios G. Papavassiliou
author_facet Panagiotis A. Konstantinopoulos
Gerasimos P. Vandoros
Michalis V. Karamouzis
Maria Gkermpesi
Georgia Sotiropoulou-Bonikou
Athanasios G. Papavassiliou
author_sort Panagiotis A. Konstantinopoulos
collection DOAJ
description Background: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-Iκ:B-α (phosphorylated Iκ:B-α), EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.
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spelling doaj-art-18873fa20ef8445daf0b69ff4dd4a4d02025-02-03T05:50:13ZengWileyCellular Oncology1570-58701875-86062007-01-0129647748210.1155/2007/831416EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGFPanagiotis A. Konstantinopoulos0Gerasimos P. Vandoros1Michalis V. Karamouzis2Maria Gkermpesi3Georgia Sotiropoulou-Bonikou4Athanasios G. Papavassiliou5Department of Biological Chemistry, Medical School, University of Athens, Athens, GreeceDepartment of Pathology, Aeghion General Hospital, Aeghion, GreeceDepartment of Biological Chemistry, Medical School, University of Athens, Athens, GreeceDepartment of Pathology, Aeghion General Hospital, Aeghion, GreeceDepartment of Anatomy and Histology–Embryology, School of Medicine, University of Patras, Patras, GreeceDepartment of Biological Chemistry, Medical School, University of Athens, Athens, GreeceBackground: COX-2 and VEGF are important triggers of colon cancer growth, metastasis and angiogenesis. Cox-2 promoter contains transcriptional regulatory elements for AP-1 and NF-κ:B transcription factors whilst vegf is a known AP-1 downstream target gene. We investigated whether stromal myofibroblasts surrounding colon adenocarcinomas express COX-2 and VEGF and whether activation of AP-1 and NF-κ:B, as well as expression of EGF-R parallel expression of COX-2 and VEGF in these cells. Methods: Immunohistochemical methodology was performed on archival sections from 40 patients with colon adenocarcinomas. We evaluated c-FOS, p-c-JUN (phosphorylated c-JUN), p-Iκ:B-α (phosphorylated Iκ:B-α), EGF-R, COX-2, NF-κ:B and VEGF expression in stromal myofibroblasts surrounding colon adenocarcinomas. Double immunostaining with a-smooth muscle actin and each antibody was done to verify the expression of these molecules in stromal myofibroblasts. Results: VEGF, p-Iκ:B-α, NF-κ:B, c-FOS, p-c-JUN, EGF-R and COX-2 were expressed in stromal myofibroblasts surrounding colon adenocarcinomas in the majority of cases. EGF-R, p-Iκ:B-α, NF-κ:B, c-FOS and p-c-JUN correlated positively with COX-2 and VEGF expression. Conclusion: Stromal myofibroblasts surrounding colon adenocarcinomas are an important source of VEGF and COX-2 production, while AP-1 and NF-κ:B transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.http://dx.doi.org/10.1155/2007/831416
spellingShingle Panagiotis A. Konstantinopoulos
Gerasimos P. Vandoros
Michalis V. Karamouzis
Maria Gkermpesi
Georgia Sotiropoulou-Bonikou
Athanasios G. Papavassiliou
EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
Cellular Oncology
title EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
title_full EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
title_fullStr EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
title_full_unstemmed EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
title_short EGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGF
title_sort egf r is expressed and ap 1 and nf κ b are activated in stromal myofibroblasts surrounding colon adenocarcinomas paralleling expression of cox 2 and vegf
url http://dx.doi.org/10.1155/2007/831416
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