BMC Cancer 2008, 8:270 http://www.biomedcentral.com/1471-2407/8/270 FHiighuerree7xpression of genes involved in O-glycan synthesis in the carcinoma compared to the papillary adenocarcinoma tumors Higher expression of genes involved in O-glycan synthesis in the carcinoma compared to the papillary adeno- carcinoma tumors. KEGG pathway analysis was performed using DAVID software. Light gray background – significantly (P < 0.05) higher expression in carcinoma; gray background – no significant difference; frame around background – over twofold dif- ference. The underlined letters C (carcinoma) or P (papillary adenocarcinoma) which follow the gene name indicate the type of tumor in which gene expression is exclusively different from the mammary gland. The direction of the arrows indicates the type of change (up- or downregulation). One arrow – statistically significant (P < 0.05) difference. Two arrows – statistically sig- nificant and over twofold difference. structural and molecular activities completes the nucleus- cytoskeleton-plasma membrane axis that comprises most of the phenotypical and functional differences between these tumors. A comparable number of genes were either upregulated or repressed in the carcinoma vs. papillary adenocarcinoma tumors, but only ~10% of these were expressed at higher levels in the papillary adenocarcinoma than in the wild- type gland. Most of these genes encode nuclear proteins that are involved in regulation of the cell cycle and responses to DNA damage and their differential expres- sion may mark the transition from a normal to neoplastic state. As discussed further on, the unique assembly of genes with this type of expression may reflect the signifi- cance of genes regulating cell sensitivity to G1 arrest in the papillary adenocarcinoma in determining the diversity among the two types of tumors. Genes that are relatively more highly expressed in the pap- illary adenocarcinoma, but at lower levels, encode cyto- plasmic proteins, many of which are specific to mammary-gland development and cell differentiation. A representative of these genes, which could potentially serve as a target for therapeutic intervention, is the proges- terone receptor (PR) which was expressed at over fourfold higher levels in the papillary adenocarcinoma compared to the carcinoma. The stronger expression of genes involved in transporter activity and ion channels in the papillary adenocarcinoma could reflect the maintenance of cell-cell contact in this loosely adhesive cell population. Page 14 of 19 (page number not for citation purposes)