Dimerization co-factor of hepatocyte nuclear factor 1/pterin-4alpha-carbinolamine dehydratase is necessary for pigmentation in Xenopus and overexpressed in primary human melanoma lesions.
Dimerization co-factor of hepatocyte nuclear factor 1 (HNF1)/pterin-4alpha-carbinolamine dehydratase (DCoH/PCD) is both a positive co-factor of the HNF1 homeobox transcription factors and thus involved in gene regulation as well as an enzyme catalyzing the regeneration of tetrahydrobiopterin. Dysfunction of DCoH/PCD is associated with the human disorders hyperphenylalaninemia and vitiligo. In Xenopus, overexpression of the protein during development induces ectopic pigmentation. In this study loss of function experiments using DCoH/PCD-specific antibodies demonstrated that the protein is also absolutely necessary for pigment cell formation in Xenopus. In normal human skin DCoH/PCD protein is weakly expressed in the basal layer of the epidermis that consists of keratinocytes and melanocytes. Whereas only 4 of 25 benign nevi reacted with DCoH/PCD-specific antibodies, high protein levels were detectable in melanoma cell lines and 13 of 15 primary malignant melanoma lesions. The comparison with the commonly used melanoma markers S100 and HMB45 demonstrated that DCoH/PCD has an overlapping but distinct expression pattern in melanoma lesions. In addition to human colon cancer, this is the second report about the overexpression of DCoH/PCD in human tumor cells indicating that the protein might be involved in cancerogenesis.
von Strandmann
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Institute of Cell Biology and Department of Dermatology, Venerology, and Allergology, University of Essen, Hufelandstrasse, Essen, Germany.
Senkel
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S
Ryffel
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Hengge
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UR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis; D004416:Dysplastic Nevus Syndrome / Q000201:enzymology; D006801:Humans; D006836:Hydro-Lyases / Q000276:immunology / Q000502:physiology*; D008545:Melanoma / Q000737:chemistry / Q000201:enzymology*; D012867:Skin / Q000201:enzymology; D012880:Skin Pigmentation; D014407:Tumor Cells, Cultured; D014981:Xenopus / Q000033:anatomy & histology / Q000196:embryology
D000906:Antibodies; D014408:Biomarkers, Tumor; D006836:Hydro-Lyases; C076392:pterin-4a-carbinolamine dehydratase