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.


CONCLUSIONS
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.
Konstantinopoulos
Panagiotis A
PA
Department of Biological Chemistry, Medical School, University of Athens, Athens, Greece.
Vandoros
Gerasimos P
GP
Karamouzis
Michalis V
MV
Gkermpesi
Maria
M
Sotiropoulou-Bonikou
Georgia
G
Papavassiliou
Athanasios G
AG
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000166:cytology; D003110:Colonic Neoplasms / Q000737:chemistry / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012189:Retrospective Studies; D017154:Stromal Cells / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D016328:NF-kappa B; D009363:Neoplasm Proteins; D018808:Transcription Factor AP-1; D042442:Vascular Endothelial Growth Factors; D051546:Cyclooxygenase 2; C512478:EGFR protein, human; D066246:ErbB Receptors