Critical role of IκB kinase alpha in embryonic skin development and skin carcinogenesis
Feng Zhu1, Eunmi Park1, Bigang Liu1, Xiaojun Xia1, Susan M. Fischer1 and Yinling Hu1,2
1Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas, USA and 2Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA.
Offprint requests to: Yinling Hu, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21701, Maryland, USA email: huy2@mail.nih.gov
Summary. 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 IKKa 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. Histol Histopathol 24, 265-271 (2009)
Key words: IκB kinase alpha (IKKα), Embryonic skin development, Skin carcinogenesis, Nuclear factor-kappaB (NF-κB)
DOI: 10.14670/HH-24.265