Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis
Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis
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核因子κB的组成型激活有助于囊性纤维化跨膜电导调节因子的表达并促进人类宫颈癌的进展和不良预后
DOI：
10.1097/igc.0b013e318292da82
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发表时间：
2013-06-01
影响因子：
4.8
通讯作者：
Hu, Lina
中科院分区：
文献类型：
--
作者：
Wu, Zhao;Peng, Xue;Hu, Lina
目的：囊性纤维化跨膜传导调节因子（CFTR）和核因子κ B（NF-κ B B）在包括宫颈癌在内的多种肿瘤的发生、发展中起重要作用。方法：采用免疫组织化学方法检测135例宫颈癌组织中CFTR和NF-κ B p65的表达，并分析其与宫颈癌发生、发展的关系。分析其与临床病理特征及预后的关系。在宫颈癌细胞系中检测到CFTR和NF-κ B B的共表达。NF-κ B p65的siRNA抑制核因子κ B信号传导，并用白细胞介素β或肿瘤坏死因子α刺激细胞激活核因子κ B信号传导。我们发现CFTR的膜表达和NF-κ B p65的核转位从正常宫颈组织、宫颈上皮内瘤变到宫颈癌均进行性增加（总体R-2 = 0.74，P < 0.001）。囊性纤维化跨膜传导调节因子表达和NF-κ B活化也与分期、组织学分级、淋巴结转移和浸润性间质深度呈正相关。多因素分析显示CFTR和NF-κ B的共表达是影响生存的独立预后因素（相对危险度为5.16; P = 0.003）。免疫荧光双标分析显示CFTR和NF-κ B B在宫颈癌中共表达。结论：囊性纤维化跨膜传导调节因子和NF-κ B在宫颈癌组织中共表达，NF-κ B的活化介导CFTR的表达。多因素分析显示CFTR和NF-κ B B的共表达与宫颈癌患者的不良预后相关。
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.