Critical role of IkB kinase alpha in embryonic skin development and skin carcinogenesis

Abstract

IκB kinase alpha (IKKα), IKKß, and IKKγ/NEMO form the IKK complex, which is essential for NF-κB activation. However, genetic studies have shown that the role of IKKα is distinct from that of IKKß or IKKγ in the development of the mouse embryonic skin. Loss of IKKα has been shown to cause epidermal hyperplasia, prevent keratinocyte terminal differentiation, and impair the formation of the skin, resulting in the deaths of IKKα-deficient (Ikkα -/-) mice soon after birth. Recent experimental data from several laboratories have revealed that IKKα functions as a tumor suppressor in human squamous cell carcinomas (SCCs) of skin, lungs, and head and neck. Chemical carcinogenesis studies using mice have shown that reduction in IKKα expression increases the number and size of Ras-initiated skin tumors and promotes their progression, indicating that reduced IKKα expression provides a selective growth advantage that cooperates with Ras activity to promote skin carcinogenesis. In this review, we will summarize these findings from our and other studies on the role that IKKα plays in development of the mouse embryonic skin and skin carcinogenesis