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

IKB kinase (IKK) alpha and beta share the function to phosphorylate IKB to activate a transcription factor NF-kappa B. Recent reports, however, revealed differences in the functions of the two kinases. The present study was designed to determine a unique function of IKK alpha on the differentiation of squamous cell carcinoma (SCC). Transfection with IKK alpha gene, but neither IKK beta nor NF-kappa B 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 IKK alpha white intracellular locatization of GFP-IKK alpha differed from that of GFP-IKK beta. Interestingly, phorbol myristate acetate together with IKKa gene transfection strongly inhibited the expression of involucrin in SCC cells and induced the phosphorylation of serine residue in IKK alpha, suggesting that protein kinase C is involved in the effect of IKK alpha on the differentiation of SCC cells. In conclusion, high expression of IKK alpha may serve as an intracellular signal to halt the epithelial differentiation of SCC cells. (c) 2005 Elsevier Ltd. ALL rights reserved.