Genetic analysis of Ras genes in epidermal development and tumorigenesis

Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mo...

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Bibliographic Details
Published in:Small GTPases 2013-10, Vol.4 (4), p.236-241
Main Authors: Drosten, Matthias, Lechuga, Carmen G, Barbacid, Mariano
Format: Article
Language:English
Subjects:
Animals
epidermis
hyperproliferation
hypoproliferation
mouse models
Ras
ras Proteins - metabolism
Signal Transduction
Skin - metabolism
squamous cell carcinoma
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Summary:Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation.
ISSN:2154-1248
2154-1256
DOI:10.4161/sgtp.26905