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

• Published in: Clinical cancer research 2005-04, Vol.11 (7), p.2518-2525
• Main Authors: BYUNG LAN LEE, HYE SEUNG LEE, JUNG, Jieun, SUNG JIN CHO, CHUNG, Hee-Yong, WOO HO KIM, JIN, Young-Woo, CHONG SOON KIM, SEON YOUNG NAM
• Format: Article
• Language: English
• Subjects: Akt; Antineoplastic agents; Biological and medical sciences; gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; NF-κB; Pharmacology. Drug treatments; prognosis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-1282

Purpose: Because the biological significance of constitutive nuclear factor-κB (NF-κB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-κB activation and its clinical significance. Experimental Design: Immunohistochemistry for NF-κB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-κB 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-κB repressor mutant of IκBα. 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-κB activation and lymphatic invasion ( P = 0.034) and a positive correlation between NF-κB activation and overall survival rate of gastric cancer patients ( P = 0.0228). In addition, NF-κB 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-κB activity in gastric cancer cells is controlled by and controls Akt. Conclusions: NF-κB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-κB activation is a valuable prognostic variable in gastric carcinoma.