Kurzfassung

Tissue homeostasis is critically regulated by cell death mechanisms which control cellular survival and proliferation through cell turn over. A dysbalance of the predominant form of controlled cell death – apoptosis – leads to alterations of tissue homeostasis and can result in acute organ failure or the emergence of cancer. Proteins involved in the regulation of tissue homeostasis have thus been implied in the emergence of disease and understanding their function is crucial to develop novel...Tissue homeostasis is critically regulated by cell death mechanisms which control cellular survival and proliferation through cell turn over. A dysbalance of the predominant form of controlled cell death – apoptosis – leads to alterations of tissue homeostasis and can result in acute organ failure or the emergence of cancer. Proteins involved in the regulation of tissue homeostasis have thus been implied in the emergence of disease and understanding their function is crucial to develop novel therapeutic approaches. The aim of this research grant is to study the role of the protoncogen B cell leukemia-3 (Bcl-3) protein in the liver during the initiation and progression of hepatocellular carcinoma (HCC) using the Cre-loxP system of organ-specific recombination. Bcl-3 controls proliferation and inflammation and preliminary results demonstrated that induced expression of Bcl-3 in CD4+ lymphocytes using the Cre-loxP System leads to spontaneous inflammation in the colon.  Since HCC is a cancer that is driven by inflammation we hypothesized that Bcl-3 could be a key player during hepatocarcinogenesis. Within the scope of this research grant, mice with Bcl-3 specific overexpression in hepatocytes are exposed to diethyl-nitrosamine (DEN) and phenobarbital and the emergence and molecular characteristics of HCC will be examined. Next to molecular regulators of cell death and proliferation a special focus will be on the role of inflammation and immune-modulatory cell types that could act as potential candidates for therapy. Additionally, metabolic pathways including insulin signaling and liponeogenesis – which have been implied in the emergence of HCC – will be studied.

 
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