Analysis of the genome in normal and in cancer mammary tissues using proteomics technologies

Klaus Czerwenka 1, Klaus Kaserer 2, Kerstin Pischinger 1, Mahmood Manavi3, Walter B. Battistutti1

1 Department of Gynecopathology, 2Department of Pathology, 3 Special Gynecology; University Hospital, Vienna, Austria

Introduction: Now that we have completed mapping the human genome, the logical next step is to determine the products of the individual genes. The expanding knowledge of the genome (DNA) and its macromolecular products (RNA, protein) is beginning to reveal that cancers can be linked to specific alterations in the molecular process of affected cells and tissues. Knowledge of the proteome has been greatly enhanced thanks to microdissection in association with the following techniques: Microarray, 2-D and MALDI. A major advantage of proteomics over genomics is the ability to analyze post-transcriptional modification. Areas where proteomics can make an impact in functional genomics are now becoming clear. Method: Some of these areas were demonstrated with samples of normal and cancerous mammary tissues analyzed using the following high-tech methods: 1.) gene discovery (microarray-techniques), 2.) annotation of the through protein data and 3-protein-protein interaction studies (2D/MALDI). Results: To date we have identified increased expression (upregulation) of cell cycle genes (Cyclin Dl, CDK4, E2F and DP2) in mammary cancer in comparison to a low expression (down-regulation) in normal mammary tissue. Therefore, in malignant tissue the proteins will make the cell dependent on growth stimuli (growth factors ) and also dependent on the protein-pathogen protein interaction. Conclusion: In this presentation we demonstrate that the combination of DNA microarray and 2D/MALDI are an emerging area in functional genomics and proteomics.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Gene Expression, Part 2.