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      NF-kappaB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix.

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          Abstract

          We demonstrate, for the first time, that the transcription factor NF-kappaB is constitutively activated during human cervical cancer progression. Immunohistochemical analysis was done using 106 paraffin-embedded cervical tissue specimens of different histological grades. In normal cervical tissue and low-grade squamous intraepithelial lesions, p50, RelA and IkappaB-alpha were mainly localized in the cytosol, whereas in high-grade lesions and squamous cell carcinomas, p50-RelA heterodimers translocated into the nucleus with a concurrent decrease in IkappaB-alpha protein. By Western blot analysis, p50 and RelA were detectable mainly in the cytosolic and nuclear extracts in normal and cancer tissues, respectively, and cytosolic IkappaB-alpha expression was detectable in normal but not in cancer cervical tissues. NF-kappaB DNA-binding activity increased during cervical cancer progression and the binding complex was mainly composed of the p50-RelA heterodimers as revealed by electrophoretic mobility shift assays. Semiquantitative RT-PCR analysis, however, showed increased levels of IkappaB-alpha mRNA in cancer samples presumably because of feedback regulation as a result of enhanced NF-kappaB DNA-binding activity and a consequent functional activation of NF-kappaB. Further immunohistochemical analysis with an antibody to phospho IkappaB-alpha revealed that phosphorylation occurs mainly in squamous intraepithelial lesions, suggesting that the IkappaB-alpha gets phosphorylated initially and degraded as the tumor progressed.

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          Author and article information

          Journal
          Oncogene
          Oncogene
          Springer Science and Business Media LLC
          0950-9232
          0950-9232
          Jan 09 2003
          : 22
          : 1
          Affiliations
          [1 ] Division of Cancer Biology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuran, Kerala, India.
          Article
          1206043
          10.1038/sj.onc.1206043
          12527907
          f23ee2b6-671b-47cc-b338-0dab702adae6
          History

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