Enhanced I kappa B kinase activity is responsible for the augmented activity of NF-kappa B in human head and neck carcinoma cells

The nuclear transcription factor kappaB (NF-kappaB) plays an important role in the development and progression of cancers. However, the mechanism by w hich cancer cells in the head and neck region acquire high NF-kappaB activi ty has not yet been clarified. In this study, we examined the NF-kappaB bin ding activity and the expression of the signal-transduction-related protein s of NF-KB in head and neck carcinoma cell lines. These cancer cells showed significantly higher NF-kappaB binding activity than normal oral epithelia l and salivary gland cells. We also demonstrated the increased phosphorylat ion and degradation of I kappaB-alpha. protein in cancer cells. Thus, enhan ced NF-kappaB activity in cancer cells is attributable to the rapid phospho rylation and degradation Of I kappaB-alpha protein. To further elucidate th e mechanism involved in this phenomenon. we analyzed both the expression le vels of upstream kinases (I kappaB kinase- (IKK-) alpha, IKK-beta. IKK-gamm a, and NF-kappaB-inducing kinase (NIK)) and the IKK activity in cells. Alth ough there was no significant difference in the expression levels of NIK, I KK-beta, or IKK-gamma in cancer cell lines compared to those in normal cell s, increased expression of IKK-alpha protein was observed in cancer cells. In addition, IKK activity was significantly augmented in cancer cells as co mpared to normal cells. Thus, our results suggest that enhanced NF-kappaB a ctivity in head and neck cancer cells may be due to the augmentation of IKK activity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.