Die Rolle von c-Fos in der Karzinogenese des hepatozellulären Karzinoms (HCC)

• Applicant: Dr. Rainer Hamacher
• Subject Area: Gastroenterology
• Term: from 2010 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169744613

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with a very poor prognosis. In hepatocarcinogenesis different pathways, like p53, Wnt/β-catenin, TGF-β, Ras, Rb, IGF-II, and transcription factors, like NF-κB, c-Myc and AP-1, are involved. I plan to analyze the role of c-Fos, a member of the AP-1 protein family, in murine and human carcinogenesis of HCC. For other members of the AP-1 protein family, especially c-Jun, the relevance in development of HCC is already demonstrated. To investigate molecular effects of c-Fos in carcinogenesis of HCC in vivo, mouse models with either conditional liver knock-out of c-Fos or inducible liver-specific ectopic expression of c-Fos will be analyzed. I also plan to examine tissue samples of human patients with the view to study the relevance of c- Fos in hepatocarcinogenesis. Furthermore, in vitro analyses of human HCC cells after knock-down or overexpression of c-Fos will be performed. Since c-Fos acts as a dimer with Jun proteins, I want in addition to investigate which of the Jun proteins interacts with c-Fos to contribute to the carcinogenesis in the liver. Therefore, I will analyze a mouse model with liver-specific overexpression of “single-chain forced Jun∼c-Fos dimers”, which functionally mimics the AP-1 protein complex.

• DFG Programme: Research Fellowships
• International Connection: Spain
• Host: Professor Dr.-Ing. Erwin F. Wagner