Introduction: Although nuclear factor-κB (NF-κB) is generally believed to be involved in carcinogenesis, the relationship between NF-κB activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-κB activation with aggressive aspects and prognosis in cervical cancer.
Methods: Nuclear factor-κB 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-κB 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-κB 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-κB nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-κB 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-κB activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-κB is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.
- Cervical cancer
- Tumor progression
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This study was supported by the Scientific and Technologic Program of the Sichuan government (grants 07FG002-018 and 2008JY0035).