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Association of constitutive nuclear factor-kappaB activation with aggressive aspects and poor prognosis in cervical cancer.

AbstractINTRODUCTION:
Although nuclear factor-kappaB (NF-kappaB) is generally believed to be involved in carcinogenesis, the relationship between NF-kappaB activation and progression of cervical cancer in clinical settings has not been reported. In this study, we investigated the association of NF-kappaB activation with aggressive aspects and prognosis in cervical cancer.
METHODS:
Nuclear factor-kappaB 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-kappaB 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-kappaB 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-kappaB nuclear translocation), and electrophoretic mobility shift assay (enhanced DNA-binding activity). In 79 cancer tissues, increased nuclear p65, an active NF-kappaB 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-kappaB activation is correlated to tumor progression, aggressive behaviors, and poor prognosis in cervical cancer, suggesting that NF-kappaB is a tumor promoter, a prognostic indicator, and a possible therapeutic target for this malignant disease.
AuthorsJinke Li, Haijun Jia, Lingxia Xie, Xuedong Wang, Xia Wang, Haining He, Yong Lin, Lina Hu
JournalInternational journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 19 Issue 8 Pg. 1421-6 (Nov 2009) ISSN: 1525-1438 [Electronic] United States
PMID20009901 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • NF-kappa B
Topics
  • Adenocarcinoma (genetics, metabolism, pathology)
  • Blotting, Western
  • Carcinoma, Squamous Cell (genetics, metabolism, pathology)
  • Cell Nucleus (metabolism)
  • Cervical Intraepithelial Neoplasia (genetics, metabolism, pathology)
  • Cervix Uteri (metabolism, pathology)
  • Electrophoretic Mobility Shift Assay
  • Female
  • Humans
  • Immunoenzyme Techniques
  • NF-kappa B (genetics, metabolism)
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Precancerous Conditions (genetics, metabolism, pathology)
  • Prognosis
  • Survival Rate
  • Uterine Cervical Neoplasms (genetics, metabolism, pathology)

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