Nuclear factor-κB activation correlates with better prognosis and Akt activation in human gastric cancer

Purpose: Because the biological significance of constitutive nuclear factor-kappa B (NF-kappa B) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappa B activation and its clinical significance. Experimental Design: Immunohistochemistry for NF-kappa B/ReIA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappa B activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappa B repressor mutant of I kappa B alpha. Results: Nuclear expression of ReIA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappa B activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappa B activation and overall survival rate of gastric canter patients (P = 0.0228). In addition, NF-kappa B activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P < 0.001), Smad4 (P = 0.002), and kangai 1 (P < 0.001) expression. An in vitro study showed that NF-kappa B activity in gastric cancer cells is controlled by and controls Akt. Conclusions: NF-kappa B activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappa B activation is a valuable prognostic variable in gastric carcinoma.