Alteration in the distribution of the epidermal protein filaggrin during two-stage chemical carcinogenesis in the SENCAR mouse skin.
The histidine-rich epidermal protein filaggrin was purified from urea extracts of newborn SENCAR mouse epidermis. The protein had a molecular weight of 28,000 and an amino acid composition distinctive for this class of proteins. The purified protein was a phosphate acceptor in an in vitro protein kinase assay. Rabbit antibodies raised against filaggrin were used in an indirect immunofluorescent survey of the distribution of filaggrin in the epidermis after single and multiple 12-O-tetradecanoylphorbol-13-acetate treatments as well as in papillomas and carcinomas. The immunofluorescent pattern of acetone-treated adult SENCAR mouse epidermis showed primarily granular layer fluorescence. A single topical 12-O-tetradecanoylphorbol-13-acetate treatment increased immunofluorescence in basal and suprabasal cells. Large papillomas produced by a dimethylbenz[a]anthracene initiation-12-O-tetradecanoylphorbol-13-acetate promotion protocol showed increased fluorescence in all layers. Exuberant papillomas showed a pleomorphic distribution of filaggrin with alternating positive and negative areas of immunofluorescence. Filaggrin immunofluorescence in invasive carcinomas was negative or only slightly positive. The distribution of filaggrin as detected by indirect immunofluorescence is a good indicator of maturation and differentiation in experimental tumors, and its presence correlates with the absence of aggressive or invasive growth.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D004817:Epidermis / Q000187:drug effects; D005260:Female; D000091344:Filaggrin Proteins; D005455:Fluorescent Antibody Technique; D005779:Immunodiffusion; D007381:Intermediate Filament Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010704:Phorbols / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D000596:Amino Acids; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate