EGF-R is expressed and AP-1 and NF-kappaB 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-kappaB 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-kappaB, 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-IkappaB-alpha (phosphorylated IkappaB-alpha), EGF-R, COX-2, NF-kappaB 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-IkappaB-alpha, NF-kappaB, 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-IkappaB-alpha, NF-kappaB, 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-kappaB transcription factors are activated and EGF-R is expressed in these cells and associated with COX-2 and VEGF production.

Medienart:

Artikel

Erscheinungsjahr:

2007

Erschienen:

2007

Enthalten in:

Zur Gesamtaufnahme - volume:29

Enthalten in:

Cellular oncology : the official journal of the International Society for Cellular Oncology - 29(2007), 6 vom: 01., Seite 477-82

Sprache:

Englisch

Beteiligte Personen:

Konstantinopoulos, Panagiotis A [VerfasserIn]
Vandoros, Gerasimos P [VerfasserIn]
Karamouzis, Michalis V [VerfasserIn]
Gkermpesi, Maria [VerfasserIn]
Sotiropoulou-Bonikou, Georgia [VerfasserIn]
Papavassiliou, Athanasios G [VerfasserIn]

Themen:

Cyclooxygenase 2
EC 1.14.99.1
EC 2.7.10.1
EGFR protein, human
ErbB Receptors
Journal Article
NF-kappa B
Neoplasm Proteins
Transcription Factor AP-1
Vascular Endothelial Growth Factors

Anmerkungen:

Date Completed 14.02.2008

Date Revised 20.10.2021

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM175303436