Resumen de Critical role of I?B kinase alpha in embryonic skin development and skin carcinogenesis
Feng Zhu, Eunmi Park, Bigang Liu, Xiaojun Xia, Susan M. Fischer, Yinling Hu
?B kinase alpha (IKK?), IKKß, and IKK?/NEMO form the IKK complex, which is essential for NF-?B activation. However, genetic studies have shown that the role of IKK? is distinct from that of IKKß or IKK? in the development of the mouse embryonic skin. Loss of IKKa has been shown to cause epidermal hyperplasia, prevent keratinocyte terminal differentiation, and impair the formation of the skin, resulting in the deaths of IKK?-deficient (Ikk?-/-) mice soon after birth. Recent experimental data from several laboratories have revealed that IKK? 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 IKK? expression increases the number and size of Ras-initiated skin tumors and promotes their progression, indicating that reduced IKK? 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 IKK? plays in development of the mouse embryonic skin and skin carcinogenesis.
