c-Jun regulates eyelid closure and skin tumor development through EGFR signaling

Dev Cell. 2003 Jun;4(6):879-89. doi: 10.1016/s1534-5807(03)00161-8.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogens / pharmacology
  • Cell Division
  • Epidermal Cells
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Epidermis / injuries
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Eyelids / abnormalities
  • Eyelids / embryology*
  • Eyelids / metabolism
  • Eyelids / ultrastructure
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Genes, jun*
  • Genetic Predisposition to Disease
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Papilloma / etiology
  • Papilloma / metabolism*
  • Papilloma / pathology
  • Signal Transduction*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transgenes


  • Carcinogens
  • Hbegf protein, mouse
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Epidermal Growth Factor
  • ErbB Receptors
  • Tetradecanoylphorbol Acetate