title: Critical role of IkappaB kinase alpha in embryonic skin development and skin carcinogenesis.
abstract: IkappaB kinase alpha (IKKalpha), IKKbeta, and IKKgamma/NEMO form the IKK complex, which is essential for NF-kappaB activation. However, genetic studies have shown that the role of IKKalpha is distinct from that of IKKbeta or IKKgamma in the development of the mouse embryonic skin. Loss of IKKalpha has been shown to cause epidermal hyperplasia, prevent keratinocyte terminal differentiation, and impair the formation of the skin, resulting in the deaths of IKKalpha-deficient (Ikkalpha-/-) mice soon after birth. Recent experimental data from several laboratories have revealed that IKKalpha 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 IKKalpha expression increases the number and size of Ras-initiated skin tumors and promotes their progression, indicating that reduced IKKalpha 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 IKKalpha plays in development of the mouse embryonic skin and skin carcinogenesis.
authors.affiliation: Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Smithville, Texas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Eunmi
authors.initials: E
authors.lastname: Park
authors.forename: Bigang
authors.initials: B
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xia
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Yinling
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D012867:Skin / Q000196:embryology*; D012878:Skin Neoplasms / Q000196:embryology* / Q000473:pathology
chemical_list: D016328:NF-kappa B; D051550:I-kappa B Kinase