Nuclear factor-kappa B regulates cyclooxygenase-2 expression and cell proliferation in human colorectal carcinoma tissue

Abstract

Objective: Activation of transcription factor nuclear factor-kappa B (NF-kappa B) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappa B is constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-kappa B in colorectal tumorigenesis, furthermore, to determine the association of RelA expression with the expression of cyclooxygenase-2 (COX-2) and tumor cell proliferation.

Methods: Paraffin sections of the normal epithelial, adenomatous and adenocarcinoma tissue were analysed immunohistochemically for RelA, COX-2, Ki-67 protein expression. EMSA (electrophoretic mobility shift assay) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The expression of COX-2 mRNA was determined by RT-PCR (reverse transcription polymerase chain reaction) analysis.

Results: Activation of NF-kappa B was significantly higher in adenocarcinoma tissue in comparison to that in adenomatous and normal epithelial tissue. The colon tumor cell proliferation, mRNA expression and protein level of COX-2 were significantly increased in the transition from normal to tumor tissue.

Conclusion: Our results suggest that NF-kappa B may promote proliferation via enhancing the expression of COX-2, and the increased expression of RelA/nuclear factor-kappa B plays an important role in the pathogenesis of colorectal carcinoma.