LOCALIZATION AND EXPRESSION OF CORNIFIN-ALPHA SPRR1 IN MOUSE EPIDERMIS, ANAGEN HAIR-FOLLICLES, AND SKIN NEOPLASMS/

Recently, cornifin-alpha/SPRR1 has been identified as a putative precu rsor protein of the cornified cell envelope, In this study, the expres sion and localization of cornifin-alpha/SPRR1 was examined in untreate d and tumor promoter-treated mouse skin, hair follicles, and skin neop lasms, Western analysis with antiserum (SQ37A) to a rabbit cornifin-al pha peptide or antiserum (SQ37C) to a human SPRR1 peptide demonstrated a 31-kDa immunoreactive protein in mouse epidermis and Northern analy sis revealed the presence of a 1-kb mRNA, Immunohistochemical staining of mouse skin with SQ37A or SQ37C revealed intense apd specific stain ing of the infundibulum, isthmus, and of Henle's layer of the inner ro of sheath of the lower anagen hair follicle and weak staining of the t elogen follicle and the suprabasal layers of the epidermis, Treatment of mouse skin with 12-O-tetradecanoylphorbol-13-acetate (TPA) produced a large increase in cornifin-alpha/SPRR1 protein and mRNA, Immunohist ochemical localization of cornifin-alpha/SPRR1 in TPA-treated skin ind icated that cornifin-alpha/SPRR1 was increased in the suprabasal epide rmis but not in the follicle, sn-1,2-Didecanoylglycerol, a model lipid second messenger, produced an increase in cornifin-alpha/SPRR1 protei n similar to that of TPA, while Mirex, a non-phorbol ester-type promot er had no effect. Topical doses of retinoic acid did not repress TPA-i nduced cornifin-alpha/SPRR1 expression, Papillomas demonstrated a 10- and 100-fold increase in cornifin-alpha/SPRR1 protein and mRNA, and ex pression was restricted to suprabasal cells, Squamous cell carcinomas exhibited an intermediate level of cornifin-alpha protein, and express ion was restricted to keratinized areas, These data indicate: i) corni fin-alpha/SPRR1 is expressed in mouse skin; ii) cornifin-alpha/SPRR1 i s localized to specific areas of the anagen hair follicle with weak st aining in the telogen follicle and epidermis; iii) epidermal cornifin- alpha/SPRR1 expression is induced by phorbol ester and sn-1,2-didecano ylglycerol but pot mirex; and iv) papillomas and squamous Cell carcino mas demonstrate a constitutive increase in cornifin-alpha/SPRR1 in dif ferentiated areas of the neoplasms.