Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7.Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene.These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.Human S100A7 or psoriasin was first identified as an over-expressed secreted protein in psoriatic skin[1]. More recently its expression in both pre-invasive (ductal carcinoma in situ, DCIS) and invasive human breast cancer was demonstrated [2]. Although highly expressed in DCIS and generally down-regulated in invasive breast cancer, the expression of psoriasin/S100A7 in both in-situ and invasive breast cancer is correlated with markers of poor prognosis [3,4] and in invasive carcinoma also with poor clinical outcome [5]. Support for psoriasin/S100A7 having a functional role in this aggressive phenotype is shown by the observation of increased growth and tumori