GLI2 is expressed in normal human epidermis and BCC and induces GLI1 expression by binding to its promoter.
Sonic hedgehog (Shh) binds to its receptor patched (PTCH), leading to the activation and repression of target genes via the GLI family of zinc-finger transcription factors. Deregulation of the Shh pathway is associated with basal cell carcinoma (BCC) due to upregulation of GLI1 and GLI2. We recently demonstrated a positive feedback loop between GLI1 and GLI2, which revealed that GLI1 may be a direct target of GLI2. Using band shift and luciferase reporter assays, we now show that GLI2 binds the GLI-binding consensus sequence in the GLI1 promoter. These data suggest that GLI2 directly activates GLI1 and that retrovirally expressed GLI2 induces expression of endogenous GLI1 in human primary keratinocytes. Finally, using in situ hybridization, we show that GLI2 is expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumor islands. These results suggest an important role for GLI2 in regulating epidermal proliferation and skin tumorigenesis.
Ikram
Mohammed S
MS
Center for Cutaneous Research, Barts and The London Queen Mary's School of Medicine & Dentistry, University of London, UK. m.s.ikram@qmul.ac.uk
Neill
Graham W
GW
Regl
Gerhard
G
Eichberger
Thomas
T
Frischauf
Anna-Maria
AM
Aberger
Fritz
F
Quinn
Anthony
A
Philpott
Mike
M
D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000473:pathology / Q000503:physiopathology*; D002460:Cell Line; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D018859:Hair Follicle / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2