Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis

Objective: Cystic fibrosis transmembrane conductance regulator (CFTR) and nuclear factor kappa B (NF-kappa B) 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-kappa B expressions in cervical cancer tissues and cell lines. Methods: The expressions of CFTR and NF-kappa B 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-kappa B was detected in cervical cancer cell lines. Nuclear factor kappa B signaling was inhibited by siRNA for NF-kappa B p65 and activated by stimulation of cells with interleukin beta or tumor necrosis factor alpha. Results: We found both the membrane expression of CFTR and nuclear translocation of NF-kappa B p65 were progressively increased from normal cervical tissue, cervical intraepithelial neoplasm, to cervical cancer (overall R-2 = 0.74, P < 0.001). Cystic fibrosis transmembrane conductance regulator expression and NF-kappa B 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-kappa B was an independent prognostic factor for survival (relative risk, 5.16; P = 0.003). Dual-immunofluorescence analysis showed CFTR and NF-kappa B were coexpressed in cervical cancer. Studies in vitro revealed that the expression levels of CFTR mRNA and protein were positively related to NF-kappa B activation. Conclusions: Cystic fibrosis transmembrane conductance regulator and NF-kappa B were coexpressed in cervical cancer, and the activation of NF-kappa B mediated the expression of CFTR. Multivariate analysis revealed that coexpression of CFTR and NF-kappa B was associated with poor prognosis in patients with cervical cancer.