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GRANATUM: A semantic social collaborative working space linking biomedical researchers, knowledge and data for the design and execution of in-silico models and experiments in cancer chemoprevention

GRANATUM is an EU-funded project with nine partners from five EU-member states, i.e. Greece, Cyprus, Ireland, Italy, Germany, and the United States of America.

The aim of the DKFZ subproject is to characterize the potential of defined small molecules identified by in silico screening to prevent breast cancer by modulating estrogen signalling and the epigenome. The workplan includes in vitro investigations on DNA methyltransferase enzyme activities, quantitative determination of DNA methylation based on mass spectrometry (MassARRAY) of candidate genes methylated during breast carcinogenesis, analyses of chromatin modifications (histone acetylation, methylation), gene re-expression analyses by quantitative RT-PCR and further detailed studies on epigenetic targets affected by the small molecules.

In the second part, a subset of compouds will be tested in vivo in the rat uterotrophic assay. Detected endpoints include the estrogen-induced change of uterine weights and gene expression, and genome-wide analyses of DNA methylation changes which may underlie morphological changes and altered estrogen response. Differentially methylated DNA regions will be enriched and analyzed by DNA array analyses or alternatively by next-generation sequenzing.

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