Keratinocyte-specific onset expression in experimental of serine protease BSSP carcinogenesis

Malignant transformation of mouse skin by chemical carcinogens and tumor pr omoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, is a multistage process leading to the formation of squamous cell carcinomas. In an effort to identify target genes whose expression is associated with skin tumorigenesis we combined elements of suppression subtractive hybridiz ation with differential screening to isolate genes that are differentially upregulated in mouse skin after short-term treatment with 12-O-tetradecanoy lphorbol-13-acetate and that exhibit a high constitutive expression in squa mous cell carcinomas. Here, we report the detailed analysis of one of these cDNAs encoding the serine protease BSSP in mouse skin. Phorbol ester appli cation increases BSSP expression in keratinocytes of the epidermis and the hair follicle several-fold starting 4 h posttreatment. Transcriptional acti vation of BSSP by 12-O-tetradecanoylphorbol-13-acetate was found to be inde pendent of c-Fos expression and resistant to downregulation by glucocortico ids. By monitoring BSSP expression throughout experimental skin carcinogene sis we found strong constitutive expression in hyperplastic epidermis as we ll as in proliferatively active keratinocytes of benign and malignant skin tumors. These results establish a novel link between expression of an as ye t ill-defined serine protease and skin carcinogenesis.