Publication: Critical role of IkB kinase alpha in embryonic skin development and skin carcinogenesis
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Date
2009
Authors
Zhu, Feng ; Park, Eunmi ; Liu, Bigang ; Xia, Xiaojun ; Fischer, Susan M. ; Hu, Yinling
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
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
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