The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma

Abstract

Background and objectives: NF-kappa B, ubiquitin and proteasome have been shown be important factors in oncogenesis. The aim of this study was to determine whether NF-kappa B could be a sensitive biomarker for gastric carcinoma.

Methods: Tumor and adjacent mucosal tissue specimens in 92 patients with gastric carcinoma were studied. The expression of NF-kappa B was evaluated by immunohistochemistry. The expression of I kappa B alpha, ubiquitin in cytoplasm and NF-kappa B in nucleoplasm was assayed by Western blot. DNA binding-activity of NF-kappa B was confirmed by electrophoretic mobility shift assay (EMSA). Fluorogenic technique was performed to measure the 26S proteasome activity.

Results: NF-kappa B positive expression in tumor tissues (82.4%) was significant higher than that in adjacent mucosal tissues (32.7%, P < 0.05). The increase of NF-kappa B activation was accompanied by the increases of ubiqutin, 26S proteasome activation and a degradation of I kappa B alpha but not the ubiquitin-conjugated I kappa B alpha/NF-kappa B complex in gastric carcinoma. NF-kappa B expression was significantly increased in patients with lymph node metastasis, TNM stage III/IV or with the habit of high intake of pickled vegetables.

Conclusions: This study demonstrates that the constitutive activation of NF-kappa B is likely due to the activation of ubiquitin-proteasome pathway and NF-kappa B can be used as a prognostic biomarker.