Abstract
To investigate the function of c-Jun during skin development and skin tumor formation, we conditionally inactivated c-jun in the epidermis. Mice lacking c-jun in keratinocytes (c-jun(Deltaep)) develop normal skin but express reduced levels of EGFR in the eyelids, leading to open eyes at birth, as observed in EGFR null mice. Primary keratinocytes from c-jun(Deltaep) mice proliferate poorly, show increased differentiation, and form prominent cortical actin bundles, most likely because of decreased expression of EGFR and its ligand HB-EGF. In the absence of c-Jun, tumor-prone K5-SOS-F transgenic mice develop smaller papillomas, with reduced expression of EGFR in basal keratinocytes. Thus, using three experimental systems, we show that EGFR and HB-EGF are regulated by c-Jun, which controls eyelid development, keratinocyte proliferation, and skin tumor formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Carcinogens / pharmacology
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Cell Division
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Epidermal Cells
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / metabolism
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Epidermis / injuries
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Eyelids / abnormalities
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Eyelids / embryology*
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Eyelids / metabolism
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Eyelids / ultrastructure
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Gene Expression Regulation, Developmental
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Gene Expression Regulation, Neoplastic
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Genes, jun*
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Genetic Predisposition to Disease
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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Mice
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Mice, Transgenic
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Models, Biological
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Papilloma / etiology
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Papilloma / metabolism*
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Papilloma / pathology
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Signal Transduction*
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Skin Neoplasms / etiology
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Skin Neoplasms / metabolism*
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Skin Neoplasms / pathology
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Tetradecanoylphorbol Acetate / pharmacology
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Transgenes
Substances
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Carcinogens
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Hbegf protein, mouse
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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Epidermal Growth Factor
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ErbB Receptors
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Tetradecanoylphorbol Acetate