B1: Role of NFATc1-NFkB crosstalk interaction in cytokine mediated progression of pancreatic cancer

Pancreatic cancer is characterized by a strong inflammatory reaction with infiltration of immune cells. We have described overexpression and activation of members of NFAT transcription factors in pancreatic cancer and demonstrated that NFATc1 exerts strong oncogenic properties through induction of G1-S phase promoting genes. We are currently investigating how NFAT themselfes are regulated on the transcriptional and posttranslational levels through signalling crosstalk. One focus of our laboratory is the identification and characterization of NFAT partner proteins in promoter binding and regulation.

Among others, we have identified a role of NFkB in NFAT signalling and transcription. We will continue this work to analyse the molecular mechanisms and functional implication of this interaction in pancreatic carcinogenesis with a specific focus on cytokine promoter regulation. For this purpose, we combine in vitro promoter binding studies (ChIP, DNAP, reporter assays, FACS, proliferation assays) with cancer inducing mice models.