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

Abstract

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‐I κ:B‐α (phosphorylated I κ: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‐I κ: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‐I κ: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.