BMC Cancer 2008, 8:270 http://www.biomedcentral.com/1471-2407/8/270 ing, heparin binding and GTP binding. These proteins assemble to regulate cell adhesion, cell death and apopto- sis, as well as cell motility. They maintain cell-cell and cell-extracellular matrix (ECM) interactions, and comple- ment system activity and apoptosis. Cluster 4 included 228 features (203 genes) which were also more highly expressed in the carcinoma, but at relatively lower levels than those in cluster 2. In the papillary adenocarcinoma, these genes were expressed at lower levels that in the wild- type tissue. These genes encode proteins which are involved with the cytoskeleton and calcium-binding activ- ities as well as IGF-I binding and chromatin binding. They complement the biological processes of better ECM-recep- tor interaction and focal adhesion shown for cluster 2, but are specifically involved in regulating actin-cytoskeleton activities and the Notch pathway. Assigning the differentially expressed genes to metabolic pathways To better understand the reasons for the differential expression of genes in the two tumor phenotypes, we dis- tinguished those which were affected by the tumorigenic process in each of the two tumor types (Figure 4). Of the 2,525 or 2,419 features (2,094 or 1,983 genes, respec- tively) that were differentially expressed in, respectively, the carcinoma or papillary adenocarcinoma tumors as compared to the mammary gland at P < 0.05, only 10 and 7%, respectively, were exclusively affected. Fifty-five and 66% of those, respectively, also showed an over twofold difference in their expression levels. We integrated this information in the following metabolic-pathway analysis. Genes that were differentially expressed in the two pheno- types were assembled into metabolic pathways (Figure 5 and Additional file 1, data sheet I). A set of genes was identified coding for distinct integrin subunits which were expressed at higher levels in carcinoma than in papillary adenocarcinoma tumors. As αβ-heterodimers, the integrins serve as receptors for ECM components, some of which (laminin and thrombospondin 1 – THBS1) are also highly expressed in the carcinoma tumors (Figure 5A). Thus, integrin α2 or α9 interacts with integrin β1 to form collagen (I, II, IV) receptors. Integrin α2 interacts with integrin β1 to form laminin or THBS1 receptors, and integrin αV interacts with integrin β3 or β5 to form RGD as well as THBS1 receptors [20,21]. All integrins except α6β4 are linked to the actin-based microfilament system, which the integrins also regulate and modulate [20]. The cytoplasmic domain of the β4 subunit is larger, connect- ing to intermediate filaments instead of to actin [20]. FCiogmurpear4ison of genes with differential expression in tumors vs. wild-type mammary gland Comparison of genes with differential expression in tumors vs. wild-type mammary gland. Genes that are exclu- sively affected in each phenotype were determined. Page 8 of 19 (page number not for citation purposes)