Expression and functional proteomic analyses of new target proteins involved in invasiveness and metastasis of breast cancer

• Applicant: Privatdozentin Dr. Annett Linge
• Subject Area: Pathology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 128047688

In a preliminary study, we have carried out proteomic profiling of membrane fractions and whole cell lysates of breast cancer cell lines with different invasive phenotypes in order to identify differentially regulated proteins. Using mass spectrometry analysis CES1 and RAD23B have been identified amongst the proteins that are differentially expressed in invasive compared to non-invasive breast cancer cells. To date, very little is known about these two proteins and their role in invasion and metastases of breast cancer cells.Our preliminary studies on CES1 and RAD23B showed that both have a functional effect on the invasive phenotype in vitro. In order to get a greater understanding of a functional role for CES1 and RAD23B in breast cancer invasion and metastasis we have set the following specific subjectives to achieve this: 1. IHC follow up on larger numbers of tissue for CES1 and RAD23B to assess their relevance in breast cancer in vivo.2. Establishment of stable CES1 and RAD23B overexpressing cell lines including assessment of phenotypic changes in order to investigate the impact of CES1 and RAD23B on the level of invasiveness.3. Localisation studies of CES1 and RAD23B in invasive and non-invasive breast cancer cell lines in order to investigate if changes in intracellular localisation are related to invasiveness.4. Proteomic characterisation of CES1 and RAD23B stable overexpressing clones that may give clues to proteins/pathways which are involved in CES1 and RAD23B related invasiveness.5. Identification of CES1 and RAD23B interacting partners/complexes that may give clues to pathways affected by CES1 and RAD23B.This further work may potentially lead to the development of novel drug therapies and specific panels of biomarkers for use as diagnostics.

• DFG Programme: Research Fellowships
• International Connection: Ireland
• Host: Professor Dr. Martin Clynes