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Association of Constitutive Nuclear Factor-κB Activation With Aggressive Aspects and Poor Prognosis in Cervical Cancer
  1. Jinke Li, MD*,,
  2. Haijun Jia, MS*,
  3. Lingxia Xie, MS*,
  4. Xuedong Wang, MS,
  5. Xia Wang, PhD,
  6. Haining He, MS,
  7. Yong Lin, PhD,§ and
  8. Lina Hu, MD*
  1. *Department of Gynecology and Obstetrics,
  2. Laboratory of Molecular and Translational Medicine, West China Second Hospital, and
  3. Department of Public Health Statistics, Sichuan University, Chengdu, Sichuan, China; and
  4. §Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM.
  1. Address correspondence and reprint requests to Lina Hu, MD, Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, 20 Renmingnan Rd, Chengdu, Sichuan 610041, China. E-mail: cqhulina2008{at}126.com.

Abstract

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.

  • NF-κB
  • Cervical cancer
  • Tumor progression
  • Metastasis
  • Prognosis

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Footnotes

  • This study was supported by the Scientific and Technologic Program of the Sichuan government (grants 07FG002-018 and 2008JY0035).

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