FOXE1, a new transcriptional target of GLI2 is expressed in human epidermis and basal cell carcinoma.
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.
Eichberger
Thomas
T
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
Regl
Gerhard
G
Ikram
Mohammed S
MS
Neill
Graham W
GW
Philpott
Michael P
MP
Aberger
Fritz
F
Frischauf
Anna-Maria
AM
D002280:Basal Cell Carcinoma / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000503:physiopathology*; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000503:physiopathology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D000075746:Zinc Finger Protein Gli2
D004268:DNA-Binding Proteins; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; C082593:GLI2 protein, human; C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2