S100A7 and the progression of breast cancer

Abstract

The S100 gene family comprises more than 20 members whose protein sequences encompass at least one EF-hand Ca2+ binding motif. The expression of individual family members is not ubiquitous for all tissues and there appears to be an element of tissue-specific expression. Molecular analysis of breast tumors has revealed that several S100s, including S100A2, S100A4 and S100A7, exhibit altered expression levels during breast tumorigenesis and/or progression. Subsequent studies have started to describe a functional role for these S100 proteins as well as their mechanism of action and the biochemical pathways they modify. The present review outlines what is known about S100A7 in breast cancer and summarizes the need to better understand the importance of this protein in breast cancer.

Figure 1

The influence of S100A7 on the prosurvival and proinvasive pathways is mediated through alterations in gene expression. The interaction of S100A7 with c-jun activation domain binding protein 1 (Jab1) results in a cellular redistribution of Jab1 to become predominately localized in the nucleus, where it stimulates gene transcription. Jab1acts as a cofactor to stimulate transcription of genes regulated by the NF-κB, activator protein-1 and HIF1 transcription factors. Extracellular S100A7 may also interact with the receptor of advanced glycation of end products (RAGE) receptor, resulting in activation of signal transduction cascades and, ultimately, activation of gene transcription. S100A7 is believed to exert its effects through Jab1 and other proteins with which it forms an interaction, and one outcome is an alteration in gene transcription.

Figure 2

Utilizing serial analysis of gene expression (SAGE) databases that are publicly available from the Cancer Genome Anatomy Project website , the expression of selected S100 genes were compared between normal and cancer breast libraries. Confirming classical laboratory methods, SAGE found the expression of S100A2 to be higher in normal tissue than in cancer tissue, as well as S100A4 being found higher in cancer tissue than in normal breast tissue. S100A7 is one of the highest expressed genes in some ductal carcinoma in situ libraries, compared with normal breast tissue where expression is almost undetectable. S100A15, which resulted from a gene duplication of S100A7, is not expressed at the same level as S100A7 in breast cancer. SAGE allows the identification and confirmation of individual gene expression levels between normal tissues and cancer tissues of the breast.