c-Jun regulates eyelid closure and skin tumor development through EGFR signaling.
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.
Zenz
Rainer
R
Research Institute of Molecular Pathology (IMP), A-1030, Vienna, Austria.
Scheuch
Harald
H
Martin
Paul
P
Frank
Carsten
C
Eferl
Robert
R
Kenner
Lukas
L
Sibilia
Maria
M
Wagner
Erwin F
EF
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
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