title: Association of constitutive nuclear factor-kappaB activation with aggressive aspects and poor prognosis in cervical cancer.
abstract: BACKGROUND
  Although nuclear factor-kappaB (NF-kappaB) is generally believed to be involved in carcinogenesis, the relationship between NF-kappaB activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-kappaB activation with aggressive aspects and prognosis in cervical cancer.
  
  
  METHODS
  Nuclear factor-kappaB subunits p65 and p50 were detected in 159 paraffin tissues including normal cervical, precancerous (squamous intraepithelial lesions), and cervical carcinoma tissues by immunohistochemistry. Nuclear factor-kappaB nuclear translocation and DNA-binding activity in precancerous or carcinoma tissues were examined by Western blot and electrophoretic mobility shift assay, respectively.
  
  
  RESULTS
  A gradual NF-kappaB activation from normal cervical epithelial cells to precancerous and carcinoma cells was detected by immunohistochemistry (nuclear expression of p65 and p50, P < 0.001), Western blot (NF-kappaB nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-kappaB form, was correlated with poor tumor grade, lymphatic metastasis, interstitial invasion, and larger tumor size (P < 0.05). Similarly, increased nuclear p50 was correlated with poor tumor grade, interstitial invasion, and larger tumor size (P < 0.05). Moreover, increased nuclear p65 was associated with lower survival rate in patients with cancer (P < 0.05).
  
  
  CONCLUSIONS
  Constitutive NF-kappaB activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-kappaB is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.
authors.affiliation: Department of Gynecology and Obstetrics, Sichuan University, Sichuan, China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Li
authors.forename: Haijun
authors.initials: H
authors.lastname: Jia
authors.forename: Lingxia
authors.initials: L
authors.lastname: Xie
authors.forename: Xuedong
authors.initials: X
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Haining
authors.initials: H
authors.lastname: He
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D016328:NF-kappa B