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Pancreatic Neoplasms: HELP
Articles by S. Jörs
Based on 1 article published since 2010
(Why 1 article?)
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Between 2010 and 2020, S. Jörs wrote the following article about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Kras(G12D) induces EGFR-MYC cross signaling in murine primary pancreatic ductal epithelial cells. 2016

Diersch, S / Wirth, M / Schneeweis, C / Jörs, S / Geisler, F / Siveke, J T / Rad, R / Schmid, R M / Saur, D / Rustgi, A K / Reichert, M / Schneider, G. ·II. Medizinische Klinik, Technische Universität München, München, Germany. · Division of Translational Solid Tumor Oncology, German Cancer Consortium (DKTK), partner site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ·Oncogene · Pubmed #26592448.

ABSTRACT: Epidermal growth factor receptor (EGFR) signaling has a critical role in oncogenic Kras-driven pancreatic carcinogenesis. However, the downstream targets of this signaling network are largely unknown. We developed a novel model system utilizing murine primary pancreatic ductal epithelial cells (PDECs), genetically engineered to allow time-specific expression of oncogenic Kras(G12D) from the endogenous promoter. We show that primary PDECs are susceptible to Kras(G12D)-driven transformation and form pancreatic ductal adenocarcinomas in vivo after Cdkn2a inactivation. In addition, we demonstrate that activation of Kras(G12D) induces an EGFR signaling loop to drive proliferation. Interestingly, pharmacological inhibition of EGFR fails to decrease Kras(G12D)-activated ERK or PI3K signaling. Instead our data provide novel evidence that EGFR signaling is needed to activate the oncogenic and pro-proliferative transcription factor c-MYC. EGFR and c-MYC have been shown to be essential for pancreatic carcinogenesis. Importantly, our data link both pathways and thereby explain the crucial role of EGFR for Kras(G12D)-driven carcinogenesis in the pancreas.