Molecules in focus
Psoriasin (S100A7)

https://doi.org/10.1016/S1357-2725(97)00066-6Get rights and content

Abstract

Psoriasin (S100A7) is a relatively new member of the S100 gene family that is located within the S100 gene cluster on chromosome 1q21 and shares the typical calcium binding domains that define this family of proteins. It was first identified as a 11.4 kDa cytoplasmic and secreted protein isolated from skin involved by psoriasis, which can be induced in cultured squamous epithelial cells. It is now known to be expressed by both normal cultured and malignant keratinocytes and malignant breast epithelial cells within ductal carcinoma in situ, suggesting an association with abnormal pathways of differentiation. Current evidence supports a role in the pathogenesis of inflammatory skin disease, as a chemotactic factor for hematopoietic cells, and a role in early stages of breast tumor progression in association with the development of the invasive phenotype. While therapeutic potential as a target for modulation of the inflammatory response in psoriasis awaits further studies, potential clinical applications already include a role as a detection marker for squamous cell carcinoma and a diagnostic marker to distinguish in situ from invasive breast cancer cells.

Introduction

Psoriasin is a relatively new member of the S100 gene family that was first identified by[9]as a 11.4 kDa protein induced in squamous epithelial cells of the epidermis isolated from skin involved by psoriasis. Psoriasin shares homology and chromosomal proximity with other members of the S100 gene family, justifying classification as S100A7. The S100 genes encode small cytoplasmic and secreted proteins that share EF-hand helix-loop-helix domains that are important for their function as calcium binding proteins[14]. Broad roles have been proposed for these genes in cell growth, differentiation and determination of cell shape.

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Structure

The Psoriasin gene maps to chromosome 1q21.2-q22, within a region that encompasses at least 12 of the S100 gene family (see Fig. 1) and several other epidermal differentiation genes1, 13. Although the gene has not been sequenced it is likely that it conforms to the organization of adjacent S100 genes. In most cases, these possess a simple three exon/two intron structure, with the first exon contributing most of the 5′ untranslated region to the mRNA and the second and third exons covering the

Biological function

Psoriasin expression is restricted to keratinocytes and breast epithelial cells, in contrast to the overlapping pattern of the related subgroup of S100 genes A8, A9 and A12, which are also expressed in hematopoietic cells of myeloid lineage. It is known to be both a cytoplasmic and secreted protein that is upregulated in keratinocytes in response to calcium and retinoic acid and during abnormal pathways of differentiation in culture, where Psoriasin is amongst the most highly induced proteins[5]

Role in pathology

The monogram Psoriasin endorses its association with psoriasis and high levels of expression in psoriasiform epidermal hyperplasia adjacent to traumatic skin ulcers have also been observed. However, the gene is clearly also expressed under conditions of abnormal epithelial differentiation and is secreted by neoplastic keratinocytes in carcinoma of the bladder[2]. More recently, Psoriasin and the related S100 A8 and A9 proteins have also been found in other abnormal epithelia, including

Role in breast cancer

Disruption of calcium signalling pathways has been implicated as a central mechanism in tumorigenesis and specifically in the process of invasion and metastasis[7]. One important component of the intracellular calcium signalling system is the S100 family of genes, which are known to be frequently expressed in breast cancer cell lines and tissues[12], but with often intriguingly different patterns of regulation that illustrate the cell type and stage-specific regulation of expression that is

In the future

It is now important to identify the receptor and/or cellular targets of a protein that is so highly expressed under certain conditions and stages of epithelial differention, in order to understand its biological function in inflammatory skin disease as well as in neoplasia. Such knowledge might on the one hand become useful in the development of new strategies to block the local epidermal inflammatory response that characterizes psoriasis, and on the other hand for the application of a clinical

Acknowledgements

This work was supported by grants from the Canadian Breast Cancer Research Initiative (CBCRI) and the U.S. Army Medical Research and Material Command (USAMRMC).

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    The expression of β-defensin-2 and -3 is upregulated by certain types of cytokines and bacteria.14,15 Some of these antimicrobial peptides may function as proto- or suppressor-oncogenes.7,16,17 Psoriasin and β-defensin-1 may be proto- and suppressor-oncogenes, respectively.18–22

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