title: Constitutive activation of nuclear factor κB contributes to cystic fibrosis transmembrane conductance regulator expression and promotes human cervical cancer progression and poor prognosis.
abstract: OBJECTIVE
  Cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor κB (NF-κB) have been known to play important roles in the development and progression of many types of cancer including cervical cancer. The study aimed to verify the relevance and significance of CFTR and NF-κB expressions in cervical cancer tissues and cell lines.
  
  
  METHODS
  The expressions of CFTR and NF-κB p65 were analyzed respectively by immunohistochemistry in total of 135 cervical tissue samples. The correlation to clinicopathologic characteristics and prognostic value was evaluated. The coexpression of CFTR and NF-κB was detected in cervical cancer cell lines. Nuclear factor κB signaling was inhibited by siRNA for NF-κB p65 and activated by stimulation of cells with interleukin β or tumor necrosis factor α.
  
  
  RESULTS
  We found both the membrane expression of CFTR and nuclear translocation of NF-κB p65 were progressively increased from normal cervical tissue, cervical intraepithelial neoplasm, to cervical cancer (overall R² = 0.74, P < 0.001). Cystic fibrosis transmembrane conductance regulator expression and NF-κB activation were also positively associated with stage, histological grade, lymph node metastasis, and invasive interstitial depth. Multivariate analysis showed that coexpression of CFTR and NF-κB was an independent prognostic factor for survival (relative risk, 5.16; P = 0.003). Dual-immunofluorescence analysis showed CFTR and NF-κB were coexpressed in cervical cancer. Studies in vitro revealed that the expression levels of CFTR mRNA and protein were positively related to NF-κB activation.
  
  
  CONCLUSIONS
  Cystic fibrosis transmembrane conductance regulator and NF-κB were coexpressed in cervical cancer, and the activation of NF-κB mediated the expression of CFTR. Multivariate analysis revealed that coexpression of CFTR and NF-κB was associated with poor prognosis in patients with cervical cancer.
authors: Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
authors: Zhao
authors: Z
authors: Wu
authors: Xue
authors: X
authors: Peng
authors: Jinke
authors: J
authors: Li
authors: Yi
authors: Y
authors: Zhang
authors: Lina
authors: L
authors: Hu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000401:mortality* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C505032:CFTR protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D008156:Luciferases