FOXE1, a new transcriptional target of GLI2 is expressed in human epidermis and basal cell carcinoma
FOXE1, a new transcriptional target of GLI2 is expressed in human epidermis and basal cell carcinoma
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DOI：
10.1111/j.0022-202x.2004.22505.x
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发表时间：
2004-05-01
影响因子：
6.5
通讯作者：
Frischauf, AM
中科院分区：
文献类型：
--
作者：
Eichberger, T;Regl, G;Frischauf, AM
Sonic hedgehog（Hh）信号传导在表皮发育和皮肤癌中起关键作用。肿瘤抑制基因patched（PTCH）的突变失活导致Hh信号通路的组成性激活，导致锌指转录因子GLI 1和GLI 2激活靶基因转录。最近在小鼠中的实验指出GLI 2是皮肤中Hh信号传导的关键介质。我们已经集中在识别候选介质的GLI 2功能在人体表皮。我们在这里表明，叉头/翼螺旋结构域转录因子FOXE 1很可能是一个直接的GLI 2靶基因。FOXE 1诱导的动力学与已知的直接靶PTCH相似，并且在报告基因测定中含有5个GLI结合位点的2.5 kb上游片段激活转录。我们通过原位杂交表明FOXE 1在毛囊的外根鞘中表达，在那里鼠Gli 2也表达。FOXE 1表达也见于人表皮的基底角质形成细胞和基底细胞癌（BCC）。这些数据表明FOXE 1在GLI 2下游的人表皮中介导Hh信号传导中的假定作用。
Sonic hedgehog (Hh) signaling plays a key role in epidermal development and skin cancer. Mutational inactivation of the tumor suppressor gene patched (PTCH) leads to constitutive activation of the Hh signaling pathway, resulting in activation of target gene transcription by the zinc finger transcription factors GLI1 and GLI2. Recent experiments in mice point to GLI2 as the key mediator of Hh signaling in skin. We have concentrated on the identification of candidate mediators of GLI2 function in the human epidermis. We show here that the forkhead/winged-helix domain transcription factor FOXE1 is likely to be a direct GLI2 target gene. The kinetics of FOXE1 induction are similar to the known direct target PTCH, and a 2.5 kb upstream fragment containing five GLI-binding sites activates transcription in a reporter assay. We show by in situ hybridization that FOXE1 is expressed in the outer root sheath of the hair follicle, where murine Gli2 is also expressed. FOXE1 expression is also found in basal keratinocytes of the human epidermis and basal cell carcinoma (BCC). These data point to a putative role of FOXE1 in mediating Hh signaling in the human epidermis downstream of GLI2.