title: Drebrin, an actin-binding, cell-type characteristic protein: induction and localization in epithelial skin tumors and cultured keratinocytes.
abstract: Isoform E2 of drebrin, an actin-binding protein originally identified in neuronal cells, has recently been identified in diverse non-neuronal cells, mostly in association with cell processes and intercellular junctions. Here, we report on the presence of drebrin in normal human skin, epithelial skin cancers, and cultured keratinocytes. Keratinocytes of normal epidermis contain almost no drebrin but the protein is readily seen in hair follicles. By immunohistochemistry and immunoblot, basal cell carcinomas (BCC) are rich in drebrin, and confocal laser scanning and immunoelectron microscopy show accumulation at adhering junctions, in co-localization with actin and partially with plaque proteins. In squamous cell carcinomas, keratoacanthomas, and in epidermal precancers, drebrin is heterogeneously distributed, appearing as mosaics. Primary keratinocyte cultures contain significant amounts of drebrin enriched at adhering junctions. When epithelium-derived cells devoid of drebrin are transfected with drebrin-enhanced green fluorescent protein, constructs accumulate in the cell periphery, and immunoprecipitation shows complexes with actin. During epidermal growth factor induced formation of cell processes, drebrin retains this junction association, as observed by live cell microscopy. Our results suggest novel functions of drebrin such as an involvement in cell-cell adhesion and tumorigenesis and a potential value in diagnosis of BCC.
authors.affiliation: Department of Dermatology, Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Wiebke K
authors.initials: WK
authors.lastname: Peitsch
authors.forename: Ilse
authors.initials: I
authors.lastname: Hofmann
authors.forename: Jutta
authors.initials: J
authors.lastname: Bulkescher
authors.forename: Michaela
authors.initials: M
authors.lastname: Hergt
authors.forename: Herbert
authors.initials: H
authors.lastname: Spring
authors.forename: Uwe
authors.initials: U
authors.lastname: Bleyl
authors.forename: Sergij
authors.initials: S
authors.lastname: Goerdt
authors.forename: Werner W
authors.initials: WW
authors.lastname: Franke
mesh_terms: D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism*; D008840:Microfilament Proteins / Q000032:analysis*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis* / Q000096:biosynthesis; D012867:Skin / Q000737:chemistry; D012878:Skin Neoplasms / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
chemical_list: D008840:Microfilament Proteins; D009479:Neuropeptides; C083795:drebrin E; D004815:Epidermal Growth Factor