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Nuclear Factor-B Activation Correlates with Better Prognosis and Akt Activation in Human Gastric Cancer

Authors' Affiliations: Department of ¹ Anatomy, Seoul National University College of Medicine, Seoul, Korea; ² Department of Pathology, Seoul National University Bundang Hospital, Gyeonggi, Korea; ³ Department of Microbiology, Hanyang University College of Medicine; ⁴ Department of Pathology, Seoul National University College of Medicine; and ⁵ Division of Radiation Effect Research, Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Seoul, Korea

Requests for reprints: Seon Young Nam, Division of Radiation Effect Research, Radiation Health Research Institute, Korea Hydro & Nuclear Power Co., Seoul 132-703, Korea. Phone: 82-2-3499-6691; Fax: 82-2-3499-6660; E-mail: seonynam{at}khnp.co.kr.

Purpose: Because the biological significance of constitutive nuclear factor-B (NF-B) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-B activation and its clinical significance.

Experimental Design: Immunohistochemistry for NF-B/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-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-B repressor mutant of IB.

Results: Nuclear expression of RelA 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-B activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-B activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-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-B activity in gastric cancer cells is controlled by and controls Akt.

Conclusions: NF-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-B activation is a valuable prognostic variable in gastric carcinoma.

Key Words: NF-B • prognosis • gastric cancer • Akt

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