核因子 κB 的组成性激活有助于囊性纤维化跨膜电导调节剂的表达，并促进人宫颈癌的进展和不良预后。
Constitutive activation of nuclear factor κB contributes to cystic fibrosis transmembrane conductance regulator expression and promotes human cervical cancer progression and poor prognosis.
机构信息
Laboratory of Biomedical Ultrasonics/Gynecological Oncology Laboratory, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
出版信息
Int J Gynecol Cancer. 2013 Jun;23(5):906-15. doi: 10.1097/IGC.0b013e318292da82.
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.
目的
囊性纤维化跨膜电导调节因子（CFTR）和核因子 κB（NF-κB）已被证实在多种癌症（包括宫颈癌）的发生和发展中发挥重要作用。本研究旨在验证 CFTR 和 NF-κB 在宫颈癌组织和细胞系中的表达相关性和意义。
方法
采用免疫组织化学方法检测 135 例宫颈癌组织标本中 CFTR 和 NF-κB p65 的表达，分析其与临床病理特征的相关性及其预后价值。检测 CFTR 和 NF-κB 在宫颈癌细胞系中的共表达，采用 NF-κB p65 siRNA 抑制 NF-κB 信号通路，用白细胞介素β或肿瘤坏死因子α刺激细胞激活 NF-κB 信号通路。
结果
我们发现 CFTR 的膜表达和 NF-κB p65 的核转位均从正常宫颈组织、宫颈上皮内瘤变逐渐增加到宫颈癌（总 R²=0.74，P<0.001）。CFTR 表达和 NF-κB 激活与分期、组织学分级、淋巴结转移和浸润间质深度也呈正相关。多因素分析显示 CFTR 和 NF-κB 的共表达是生存的独立预后因素（相对风险 5.16；P=0.003）。双重免疫荧光分析显示 CFTR 和 NF-κB 在宫颈癌中存在共表达。体外研究表明 CFTR mRNA 和蛋白的表达水平与 NF-κB 的激活呈正相关。
结论
CFTR 和 NF-κB 在宫颈癌中存在共表达，NF-κB 的激活介导了 CFTR 的表达。多因素分析显示 CFTR 和 NF-κB 的共表达与宫颈癌患者的不良预后相关。
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