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

Konstantinopoulos, PanagiotisVandoros, Gerasimos P.Karamouzis, Michalis V.Gkermpesi, MariaSotiropoulou-Bonikou, GeorgiaPapavassiliou, Athanasios G.2016-02-012007Konstantinopoulos, Panagiotis A., Gerasimos P. Vandoros, Michalis V. Karamouzis, Maria Gkermpesi, Georgia Sotiropoulou-Bonikou, and Athanasios G. Papavassiliou. 2007. “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 : the Official Journal of the International Society for Cellular Oncology 29 (6): 477-482. doi:10.1155/2007/831416. http://dx.doi.org/10.1155/2007/831416.1570-5870http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983928Background:: 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.en-USColon adenocarcinomastromal myofibroblastsEGF-RAP-1NF-COX-2VEGFEGF-R is Expressed and AP-1 and NF-κ:B Are Activated in Stromal Myofibroblasts Surrounding Colon Adenocarcinomas Paralleling Expression of COX-2 and VEGFJournal Article2016-02-0110.1155/2007/831416