Nakayama Hideki, Ikebe Tetsuro, Shirasuna Kanemitsu
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.
Oral Oncol. 2005 Aug;41(7):729-37. doi: 10.1016/j.oraloncology.2005.03.013.
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.
IκB激酶（IKK）α和β具有共同的功能，即磷酸化IκB以激活转录因子NF-κB。然而，最近的报道揭示了这两种激酶在功能上的差异。本研究旨在确定IKKα在鳞状细胞癌（SCC）分化中的独特功能。用IKKα基因转染，但不用IKKβ或NF-κB基因转染，可抑制培养的SCC细胞中组成型表达以及细胞外钙诱导的外皮蛋白和角蛋白聚集素（上皮分化标志物）的表达。在稳定表达绿色荧光蛋白（GFP）融合的IKKα的SCC细胞中可见从多边形到成纤维细胞形状的形态变化，而GFP-IKKα的细胞内定位与GFP-IKKβ不同。有趣的是，佛波酯肉豆蔻酸酯与IKKα基因转染一起强烈抑制SCC细胞中外皮蛋白的表达，并诱导IKKα中丝氨酸残基的磷酸化，这表明蛋白激酶C参与了IKKα对SCC细胞分化的作用。总之，IKKα的高表达可能作为一种细胞内信号来阻止SCC细胞的上皮分化。
