S100S PROTEIN EXPRESSION IN A LARGE SAMPLE-SET OF BREAST CANCER TISSUES

S100 proteins are low molecular weight proteins ranging in size from 9 to 13 kDa. They form homo- andheterodimers and even oligomers and are expressed in tissue and cell-specific manner [1]. It is well documented,infact, that S100 proteins have a broad range of intracellular and extracellular functions. Intracellular functionsinclude regulation of protein phosphorylation, enzyme activity, calcium homeostasis, regulation of cytoskeletalcomponents and regulation of transcriptional factors, so they are involved in several biological processes includingcell cycle regulation, cell growth, cell differentiation, and motility [2]. Extracellularly they act in a cytokine likemanner through the receptor for advanced glycation end products (RAGE). In consideration of the critical rolesplayed by S100 proteins in such large spectrum of biological activities, is not surprising that improper expression ofS100 members is correlated with many pathologies and especially with cancer. A number of S100 proteins havebeen shown to interact with oncogenes and various proteins involved in cancer progression, including p53,cytoskeletal proteins, MMPs, and others [3,4].In this study we aimed to perform a large-scale proteomic investigation on breast cancer patients for thescreening of multiple forms of S100 proteins.The 100 surgical tissues of ductal infiltrating breast cancer utilized were collected between 2003 and 2007 inthe Breast Unit of the La Maddalena Hospital. Tissue extracts were submitted to proteomic preparations for2D-IPGand protein identification was performed by peptide mass finger printing.The S100 protein members identified in different proteomic maps were: S100A2 (protein S-100L), S100A4(metastasin), S100A6 (Calcyclin, Prolactin receptor-associated protein), two isoforms, S100A7 (psoriasin), twoisoforms, S100A8 (Calgranulin-A),S100A11 (Calgizzarin), three isoforms andS100A13 (S100 calcium-binding proteinA13) (Fig. 1). Our results have shown thatthe majority of S100 proteins were presentat very low levels, if not absent, in the nontumoraltissues adjacent to the primarytumor. Moreover, we showed that someS100 protein members were ubiquitouslyexpressed in almost all patients, whileothers appeared more sporadic among thesame group of patients. The Associationanalysis of S100 members with tumorvariables (age, tumor size, nodal status, immuno-cytochemical, presence of HER-2, oestrogen receptors,progesterone receptor, and Ki67), showed no significant correlations of except for S100A6 (isoform b) andS100A13 correlating with Ki67. More interestingly, patients which developed distant metastases after a three yearfollow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. Themost robust correlation with metastasis regarded primarily the protein S100A4, and secondly the protein S100A7.We believe that this information may substantially contribute to the progress of protein profiling of breastcancer and help to organize subclasses for clinical applications.