Prof. Dr. med. Hans H. Kreipe, Dr. rer. nat. Andreas Pich
Institute of Pathology
Protein profiling of human breast cancer We are interested in the alterations of protein and peptide profiles in morphologically well defined breast specimens on a proteome wide scale. Differences in the protein and peptide pattern of e. g. normal breast epithelial cells and tumor cells should lead to the identification of proteins which are specific to tumors, might be used as new tumor markers or might contribute to a better understanding of tumor development.
Breast cancer is the leading course of cancer mortality in females. In Germany nearly 45,000 females develop the disease per year and one third will die from it. Prediction of aggressiveness of individual cases pose a particular problem in this type of cancer. Morphologically identical cancers show different biological behaviour in terms of aggressiveness, progression, and response to therapy. DNA-array technology and protein/peptide profiling provide novel instruments to uncover tumor heterogeneity and to identify prognostically distinct subclasses of breast cancer. In our laboratory we employ modern proteomic techniques like HPLC and mass spectrometry to establish peptide and protein maps of different breast specimens.
Since all tumor cells are surrounded by stroma cells, lymphocytes, and cells from the vascular system all protein/peptide extracts of solid tumors are contaminated with proteins and peptides from normal cells. Using laser capture microdissection, morphologically defined tumor cells can be isolated from histological tissue preparations. Subsequently, they can be analyzed to establish truly cell-specific protein and peptide profiles.
In the proposed project, protein and peptide profiles should be generated from microdissected breast cells. Normal breast epithelial cells, precancerous lesions of epithelial cells, intraductal- and invasive carcinomas of the breast will be analyzed and the protein and peptide pattern of these different samples will be compared. Proteins specific for tumor cells will be identified and characterized. Their suitability as tumor marker and their possible function in breast cancer will be established.
A complementary project will be the quantification of known proteins in breast cancer specimens for which it had been shown that their expression, or amplification status is altered during tumor development.
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