c-Jun regulates eyelid closure and skin tumor development through EGFR signaling
c-Jun regulates eyelid closure and skin tumor development through EGFR signaling
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DOI：
10.1016/s1534-5807(03)00161-8
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发表时间：
2003-06-01
影响因子：
11.8
通讯作者：
Wagner, EF
中科院分区：
文献类型：
--
作者：
Zenz, R;Scheuch, H;Wagner, EF
为了研究c-Jun在皮肤发育和皮肤肿瘤形成过程中的作用，我们对表皮中的c-Jun进行了条件灭活。角质形成细胞中缺乏c-jun（c-jun(Deltaep)）的小鼠发育正常皮肤，但眼睑中EGFR表达水平降低，导致出生时眼睛张开，在EGFR缺失的小鼠中观察到。c-jun（Deltaep）小鼠的原代角质形成细胞增殖不良，分化增加，形成突出的皮质肌动蛋白束，很可能是因为EGFR及其配体HB-EGF的表达减少。在缺乏c-Jun的情况下，易患肿瘤的K5-SOS-F转基因小鼠发生较小的乳头状瘤，基底角化细胞中EGFR的表达降低。因此，通过三个实验系统，我们发现EGFR和HB-EGF受c-Jun调控，c-Jun控制眼睑发育、角质细胞增殖和皮肤肿瘤形成。
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.