Functional characterization of Bcl-3 in pancreatic cancer

• Applicant: Professor Dr. Hana Algül
• Subject Area: Gastroenterology
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 225362146

Pancreatic ductal adenocarcinoma (PDAC) remains one of the tumors with the worst prognosis. In addition to early metastasis strong resistance toward radiation and chemotherapy account for the still very high mortality of this disease. Identification of new therapeutically relevant signaling pathways is therefore among others the focus of current research activities. Together with other research groups we identified the Jak2 / Stat3 signaling pathway as a relevant target in the treatment of pancreatic cancer. With the help of the first funding period we worked up the mechanisms of peristenten Stat3 activation using various genetic models. We furhter observed an interference of Stat3 activation with the expression of Bcl-3, an atypical protein IkappaB. The relevance of this protein for pancreatic carcinogenesis has not been studied. In preliminary work we were able to demonstrate that Bcl-3 is detectable not only in most human cancer cell lines, but also in pancreatic specimens. Its genetic inactivation in murine mouse model reveals a tumorsuppressive role. Deletion of Bcl-3 leads to a pronounced metastasis of pancreatic cancer. The focus of this proposal is therefore the exact investigation of interference between Bcl-3 and Stat3 and its relevance. We will also characterize the function of Bcl-3 as a tumorsuppressor. In the long term, we hope this project deepens our understanding og the role of the Bcl-3/Stat3 axis in the pathophysiology and treatment of pancreatic cancer.

• DFG Programme: Research Grants