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

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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.
AdolescentAdultAgedAged, 80 and overAndrostadienes/pharmacologyBlotting, WesternCell Line, TumorChildChild, PreschoolChromones/pharmacologyEnzyme ActivationFemaleGene Expression Regulation, Neoplastic/drug effectsGenetic Vectors/geneticsHumansImmunohistochemistryInfantInfant, NewbornLuciferases/genetics/metabolismMaleMiddle AgedMorpholines/pharmacologyNF-kappa B/analysis/genetics/*metabolismNeoplasm StagingPrognosisProtein-Serine-Threonine Kinases/genetics/*metabolismProto-Oncogene Proteins/genetics/*metabolismProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2/analysisRNA, Messenger/genetics/metabolismRecombinant Fusion Proteins/genetics/metabolismRetroviridae/geneticsReverse Transcriptase Polymerase Chain ReactionStomach Neoplasms/genetics/metabolism/*pathologySurvival AnalysisTissue Array AnalysisTranscription Factor RelATransfectionTumor 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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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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