Enhanced IkappaB kinase activity is responsible for the augmented activity of NF-kappaB 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 which cancer cells in the head and neck region acquire high NF-kappaB activity has not yet been clarified. In this study, we examined the NF-kappaB binding activity and the expression of the signal-transduction-related proteins of NF-kappaB in head and neck carcinoma cell lines. These cancer cells showed significantly higher NF-kappaB binding activity than normal oral epithelial and salivary gland cells. We also demonstrated the increased phosphorylation and degradation of IkappaB-alpha protein in cancer cells. Thus, enhanced NF-kappaB activity in cancer cells is attributable to the rapid phosphorylation and degradation of IkappaB-alpha protein. To further elucidate the mechanism involved in this phenomenon, we analyzed both the expression levels of upstream kinases (IkappaB kinase- (IKK-) alpha, IKK-beta, IKK-gamma, and NF-kappaB-inducing kinase (NIK)) and the IKK activity in cells. Although there was no significant difference in the expression levels of NIK, IKK-beta, or IKK-gamma in cancer cell lines compared to those in normal cells, increased expression of IKK-alpha protein was observed in cancer cells. In addition, IKK activity was significantly augmented in cancer cells as compared to normal cells. Thus, our results suggest that enhanced NF-kappaB activity in head and neck cancer cells may be due to the augmentation of IKK activity.
Tamatani
T
T
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. ttama@dent.tokushima-u.ac.jp
Azuma
M
M
Aota
K
K
Yamashita
T
T
Bando
T
T
Sato
M
M
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human