Effects of IκB kinase α on the differentiation of squamous carcinoma cells

IκB kinase (IKK) α and β share the function to phosphorylate IκB to activate a transcription factor NF-κB. Recent reports, however, revealed differences in the functions of the two kinases. The present study was designed to determine a unique function of IKKα on the differentiation of squamous cell carcinoma (SCC). Transfection with IKKα gene, but neither IKKβ nor NF-κB 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 IKKα while intracellular localization of GFP-IKKα differed from that of GFP-IKKβ. Interestingly, phorbol myristate acetate together with IKKα gene transfection strongly inhibited the expression of involucrin in SCC cells and induced the phosphorylation of serine residue in IKKα, suggesting that protein kinase C is involved in the effect of IKKα on the differentiation of SCC cells. In conclusion, high expression of IKKα may serve as an intracellular signal to halt the epithelial differentiation of SCC cells.