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TY - JOUR AU - Nair, Asha AU - Venkatraman, Manickam AU - Maliekal, Tessy T AU - Nair, Balaraman AU - Karunagaran, Devarajan PY - 2003 DA - 2003/01/01 TI - NF-κB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix JO - Oncogene SP - 50 EP - 58 VL - 22 IS - 1 AB - We demonstrate, for the first time, that the transcription factor NF-κB 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 IκB-α 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 IκB-α 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 IκB-α expression was detectable in normal but not in cancer cervical tissues. NF-κB 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 IκB-α mRNA in cancer samples presumably because of feedback regulation as a result of enhanced NF-κB DNA-binding activity and a consequent functional activation of NF-κB. Further immunohistochemical analysis with an antibody to phospho IκB-α revealed that phosphorylation occurs mainly in squamous intraepithelial lesions, suggesting that the IκB-α gets phosphorylated initially and degraded as the tumor progressed. SN - 1476-5594 UR - https://doi.org/10.1038/sj.onc.1206043 DO - 10.1038/sj.onc.1206043 ID - Nair2003 ER -