title: c-Jun regulates eyelid closure and skin tumor development through EGFR signaling.
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.
authors.affiliation: Research Institute of Molecular Pathology (IMP), A-1030, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Zenz
authors.forename: Harald
authors.initials: H
authors.lastname: Scheuch
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Carsten
authors.initials: C
authors.lastname: Frank
authors.forename: Robert
authors.initials: R
authors.lastname: Eferl
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.forename: Erwin F
authors.initials: EF
authors.lastname: Wagner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000293:injuries; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005143:Eyelids / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D016758:Genes, jun; D020022:Genetic Predisposition to Disease; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010212:Papilloma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019076:Transgenes
chemical_list: D002273:Carcinogens; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D013755:Tetradecanoylphorbol Acetate