S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer
- Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young
- Issue Date
- American Association for Cancer Research
- Clin Cancer Res 2005;11(7):2518-25.
- Adolescent; Adult; Aged; Aged, 80 and over; Androstadienes/pharmacology; Blotting, Western; Cell Line, Tumor; Child; Child, Preschool; Chromones/pharmacology; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic/drug effects; Genetic Vectors/genetics; Humans; Immunohistochemistry; Infant; Infant, Newborn; Luciferases/genetics/metabolism; Male; Middle Aged; Morpholines/pharmacology; NF-kappa B/analysis/genetics/*metabolism; Neoplasm Staging; Prognosis; Protein-Serine-Threonine Kinases/genetics/*metabolism; Proto-Oncogene Proteins/genetics/*metabolism; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2/analysis; RNA, Messenger/genetics/metabolism; Recombinant Fusion Proteins/genetics/metabolism; Retroviridae/genetics; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms/genetics/metabolism/*pathology; Survival Analysis; Tissue Array Analysis; Transcription Factor RelA; Transfection; Tumor Suppressor Proteins/analysis
- PURPOSE: Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. EXPERIMENTAL DESIGN: Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB 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-kappaB repressor mutant of IkappaBalpha. 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-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB 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-kappaB activity in gastric cancer cells is controlled by and controls Akt. CONCLUSIONS: NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.
- 1078-0432 (Print)
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