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Oncogenic transformations lead to profound alterations of cellular metabolism. These metabolic changes do not only support tumor cell growth and proliferation but also contribute to malignity and tumor progression.

In collaboration with the group of Prof. Hengstler at the Leibniz Research Centre for Working Environment and Human Factors at the TU-Dortmund (IfADo) we are currently investigating how an ERBB2 oncogenic transformation can alter cellular metabolism and how this metabolic reprogramming contributes to tumor properties such as chemoresistance and survival capacity. For this purpose we are applying an MCF-7 breast cancer cell line with a Tet-on inducible expression of an oncogenic variant of ERBB2 (NeuT).

Analysis of genome-wide transcriptional events by microarrays and realtime PCR revealed changes in the mRNA level of numerous enzymes involved in different pathways such as carbohydrate, folate and polyamine metabolism, lipid homeostasis, de novo synthesis of nucleotides and redox status [1]. Mass spectrometry-based profiling techniques are established at ISAS [2] which allow a relative quantification of key metabolites and a comprehensive analysis of glycerophospholipid species in not-transformed and ERBB2-transformed breast cancer cells.

[1] Cadenas C et al., Role of thioredoxin reductase 1 and thioredoxin interacting protein (TXNIP) in prognosis of breast cancer, Breast Cancer Res, 2010, submitted.

[2] Hein EM et al., Glycerophospholipid profiling by high-performance liquid
chromatography/ mass spectrometry using exact mass measurements and multi-stage mass spectrometric fragmentation experiments in parallel, Rapid Commun. Mass Spectrom, 23, 2009, 1636-1646