BMC Cancer 2008, 8:270 http://www.biomedcentral.com/1471-2407/8/270 transgenic Stat5 variant which was involved in inducing the tumors. The clinical relevance of our findings is an important issue. To the best of our knowledge, no corresponding comparative study has been performed in breast tumors that would allow direct alignment with our data. How- ever, information suggests that the poorly differentiated DCIS (grade III) is more likely to be associated with inva- sive human disease than its well-differentiated (grade I) counterparts [12,53-55]. This may be reflected in the higher motility implied by the analysis of the poorly dif- ferentiated carcinoma compared to the highly differenti- ated papillary adenocarcinoma. On an individual gene basis, our data match the results presented in a study determining gene-expression profiles during the transi- tion of breast tumors to invasive stages [56]. The mouse and human lists shared over 30 genes or close family members with higher expression in the high-grade, less differentiated tumors. These include proteosome 26 sub- unit (PSMD), topoisomerase (TOP), reticulon 4 (RTN4) and CDK, among others. Gene-expression profiles have also been compared in human papillary thyroid carcino- mas at different levels of differentiation [57]. In the aggressive, less differentiated groups, a similar increase in the expression of genes encoding the collagen proteins was noted, as well as in those encoding CDC7, TOP2, UBE2 and Rho. In contrast, ESP8 and members of the ker- atin family were downregulated. The above studies pro- vide lists of genes that were affected by the degree of tumor differentiation. Our data link these genes to a mechanistic base and involve putative pathways that may enable more successful therapeutic intervention. Conclusion Gene-expression profiling in the carcinoma and papillary adenocarcinoma tumors pinpointed distinct molecular functions and major metabolic pathways that are imple- mented in each tumor to preserve its unique structure and functions. The array data associated the papillary adeno- carcinoma with increased expression of genes involved in cell-cell contact and cell-cycle control at an early cell-cycle stage. The carcinoma tumors, on the other hand, dis- played increased expression of pathways whose genes are involved in mediating cell-ECM interactions, detachment, motility and spreading. Only a fraction of the genes com- posing a particular pathway were affected. This suggests a dominant role for their encoded proteins in determining specific tumor properties at this basic gene-expression level. Additional proteomic analysis is expected to com- plement this study by linking a catalytic activity, mediated by post-transcriptional modifications, to the differential expression of these genes. Abbreviations GO: gene ontology. ECM: extracellular matrix. H&E: hematoxylin & eosin. RT-PCR: reverse-transcription PCR. Stat: signal transducer and activator of transcription. STAT5: transgenic Stat5. Competing interests These authors declare that they have no competing inter- ests. Authors' contributions TE designed and performed the research and also helped in writing the manuscript. IB designed the research and wrote the manuscript. Additional material Additional file 1 Sheet A. List of primers used to amplify coding regions of the following listed genes. Sheet B. List of features with significantly (P ≤ 0.05) differ- ent levels of expression in the carcinoma vs. papillary adenocarcinoma tumors. Sheet C. List of features with significant (P ≤ 0.05) and an over twofold difference in expression in the carcinoma vs. papillary adenocar- cinoma tumors. Sheet D. GO classification: List of genes comprising the cellular component analysis. Sheet E. GO classification: List of genes com- prising the molecular function analysis. Sheet F. GO classification: List of genes comprising the biological process analysis. Sheet G. List of genes with significant (P ≤ 0.05) and an over twofold difference in expression in carcinoma vs. papillary adenocarcinoma tumors comprising the four clusters. Sheet H. List of genes included in the DAVID GO analysis of the four clusters. Sheet I. List of genes with differential expression in the car- cinoma and papillary adenocarcinoma tumors that were assembled into the distinct metabolic pathways. Click here for file [http://www.biomedcentral.com/content/supplementary/1471- 2407-8-270-S1.xls] Acknowledgements We thank Dr. Ron Ofir (Weizmann Institute of Science, Rehovot, Israel) for his help in the bioinformatics analysis and Dr. M. Reichenstein for helpful suggestions and technical support. This study was supported by a grant from the Israel Science Foundation, Israel Academy of Sciences, contract number: 706/04 to Itamar Barash. Contribution No. 506/07 from the ARO, The Volcani Center, Bet-Dagan, Israel. References 1. Grigoriadis A, Mackay A, Reis-Filho JS, Steele D, Iseli C, Stevenson BJ, Jongeneel CV, Valgeirsson H, Fenwick K, Iravani M, Fenwick K, Weber B, Hardisson D, Schmitt FC, Palacios J, Lakhani SR, Ashworth A: Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data. Breast Cancer Res 2006, 8:R56-R71. 2. 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