Association of Constitutive Nuclear Factor-kappa B Activation With Aggressive Aspects and Poor Prognosis in Cervical Cancer

作者：Li Jinke; Jia Haijun; Xie Lingxia; Wang Xuedong; Wang Xia; He Haining; Lin Yong; Hu Lina^*

来源：International Journal of Gynecological Cancer, 2009, 19(8): 1421-1426.

DOI：10.1111/IGC.0b013e3181b70445

• NF-kappa B
• Cervical cancer
• Tumor progression
• Metastasis
• Prognosis

Introduction: Although nuclear factor-kappa B (NF-kappa B) is generally believed to be involved in carcinogenesis, the relationship between NF-kappa B activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-kappa B activation with aggressive aspects and prognosis in cervical cancer.
Methods: Nuclear factor-kappa B 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-kappa B 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-kappa B 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-kappa B nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-kappa B 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-kappa B activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-kappa B is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.

• 出版日期2009-11
• 单位四川大学