Enhanced IkappaB kinase activity is responsible for the augmented activity of NF-kappaB in human head and neck carcinoma cells.

Abstract

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.

• Authors: T Tamatani, M Azuma, K Aota, T Yamashita, T Bando, M Sato
• Journal: Cancer letters (Cancer Lett) Vol. 171 Issue 2 Pg. 165-72 (Oct 10 2001) ISSN: 0304-3835 [Print] Ireland
• PMID: 11520600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• NF-kappa B
• NF-kappa B p50 Subunit
• RNA, Messenger
• Transcription Factor RelA
• Protein Serine-Threonine Kinases
• CHUK protein, human
• I-kappa B Kinase
• IKBKB protein, human
• IKBKE protein, human

Topics

• Carcinoma, Squamous Cell (enzymology, metabolism)
• Head and Neck Neoplasms (enzymology, metabolism)
• Humans
• I-kappa B Kinase
• Isoenzymes (biosynthesis, metabolism)
• NF-kappa B (biosynthesis, metabolism)
• NF-kappa B p50 Subunit
• Phosphorylation
• Protein Binding
• Protein Serine-Threonine Kinases (biosynthesis, genetics, metabolism)
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factor RelA
• Tumor Cells, Cultured