Effects of IkappaB kinase alpha on the differentiation of squamous carcinoma cells.
IkappaB kinase (IKK) alpha and beta share the function to phosphorylate IkappaB to activate a transcription factor NF-kappaB. Recent reports, however, revealed differences in the functions of the two kinases. The present study was designed to determine a unique function of IKKalpha on the differentiation of squamous cell carcinoma (SCC). Transfection with IKKalpha gene, but neither IKKbeta nor NF-kappaB gene, inhibited the constitutive expressions as well as extracellular calcium-induced expressions of involucrin and filaggrin, epithelial differentiation markers, in cultured SCC cells. Morphological changes from polygonal to fibroblastic shape were seen in the SCC cells stably expressing green-fluorescent protein (GFP)-fused IKKalpha while intracellular localization of GFP-IKKalpha differed from that of GFP-IKKbeta. Interestingly, phorbol myristate acetate together with IKKalpha gene transfection strongly inhibited the expression of involucrin in SCC cells and induced the phosphorylation of serine residue in IKKalpha, suggesting that protein kinase C is involved in the effect of IKKalpha on the differentiation of SCC cells. In conclusion, high expression of IKKalpha may serve as an intracellular signal to halt the epithelial differentiation of SCC cells.
Department of Oral and Maxillofacial Surgery, Sensory and Motor Organ Sciences, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Hideki
H
Nakayama
Tetsuro
T
Ikebe
Kanemitsu
K
Shirasuna
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D000091344:Filaggrin Proteins; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000037:antagonists & inhibitors; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D011498:Protein Precursors / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; C032253:involucrin; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase