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.
Original language | English |
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Pages (from-to) | 879-89 |
Number of pages | 11 |
Journal | Developmental Cell |
Volume | 4 |
Issue number | 6 |
Publication status | Published - Jun 2003 |
Keywords
- Animals
- Apoptosis
- Carcinogens
- Cell Division
- Epidermal Growth Factor
- Epidermis
- Eyelids
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Neoplastic
- Genes, jun
- Genetic Predisposition to Disease
- Intercellular Signaling Peptides and Proteins
- Mice
- Mice, Transgenic
- Models, Biological
- Papilloma
- Receptor, Epidermal Growth Factor
- Signal Transduction
- Skin Neoplasms
- Tetradecanoylphorbol Acetate
- Transgenes